[ { "text": "Mathematics of nerve signals: Mathematical models describing the signals propagating in nerve fibres are\ndescribed. The emphasis is on the mathematical structures of governing\nequations while the extremely rich physiological aspects are here not analysed.\nBased on models of single waves, a joint coupled model is presented which is\nable to describe the action potential and the accompanying mechanical effects\ntogehter with temperature changes within one system of partial differential\nequations. The whole signal is an ensemble which includes primary and secondary\ncomponents. The primary components of a signal are the action potential itself\nand longitudinal mechanical waves in axoplasm and surrounding biomembrane.\nThese components are characterized by corresponding velocities. The secondary\ncomponents of a signal are derived from primary components and include\ntransverse displacement of a biomembrane and the temperature change. These\nsecondary components have no independent velocities in the presented model.", "category": "physics_bio-ph" }, { "text": "Error Catastrophe Can Be Avoided by Proofreading Innate to\n Template-Directed Polymerization: An important issue for the origins of life is ensuring the accurate\nmaintenance of information in replicating polymers in the face of inevitable\nerrors. Here, we investigated how this maintenance depends on reaction kinetics\nby incorporating the elementary steps of polymerization into the population\ndynamics of polymers. We found that template-directed polymerization entails an\ninherent error-correction mechanism akin to kinetic proofreading, generating\nlong polymers that are more tolerant to an error catastrophe. Because this\nmechanism does not require enzymes, it is likely to operate under broad\nprebiotic conditions.", "category": "physics_bio-ph" }, { "text": "Network modules help the identification of key transport routes,\n signaling pathways in cellular and other networks: Complex systems are successfully reduced to interacting elements via the\nnetwork concept. Transport plays a key role in the survival of networks. For\nexample the specialized signaling cascades of cellular networks filter noise\nand efficiently adapt the network structure to new stimuli. However, our\ngeneral understanding of transport mechanisms and signaling pathways in complex\nsystems is yet limited. Here we summarize the key network structures involved\nin transport, list the solutions available to overloaded systems for relaxing\ntheir load and outline a possible method for the computational determination of\nsignaling pathways. We highlight that in addition to hubs, bridges and the\nnetwork skeleton, the overlapping modular structure is also essential in\nnetwork transport. Moreover, by locating network elements in the space of\noverlapping network modules and evaluating their distance in this \"module\nspace\", it may be possible to approximate signaling pathways computationally,\nwhich, in turn could serve the identification of signaling pathways of complex\nsystems. Our model may be applicable in a wide range of fields including\ntraffic control or drug design.", "category": "physics_bio-ph" }, { "text": "Search efficiency of biased migration towards stationary or moving\n targets in heterogeneously structured environments: Efficient search acts as a strong selective force in biological systems\nranging from cellular populations to predator-prey systems. The search\nprocesses commonly involve finding a stationary or mobile target within a\nheterogeneously structured environment where obstacles limit migration. An open\ngeneric question is whether random or directionally biased motions or a\ncombination of both provide an optimal search efficiency and how that depends\non the motility and density of targets and obstacles. To address this question,\nwe develop a simple model that involves a random walker searching for its\ntargets in a heterogeneous medium of bond percolation square lattice and used\nmean first passage time (MFPT, $\\langle T \\rangle$) as an indication of average\nsearch time. Our analysis reveals a dual effect of directional bias on the\nminimum value of $\\langle T \\rangle$. For a homogeneous medium, directionality\nalways decreases $\\langle T \\rangle$ and a pure directional migration (a\nballistic motion) serves as the optimized strategy; while for a heterogeneous\nenvironment, we find that the optimized strategy involves a combination of\ndirected and random migrations. The relative contribution of these modes is\ndetermined by the density of obstacles and motility of targets. Existence of\nrandomness and motility of targets add to the efficiency of search. Our study\nreveals generic and simple rules that govern search efficiency. Our findings\nmight find application in a number of areas including immunology, cell biology,\nand ecology.", "category": "physics_bio-ph" }, { "text": "Bacteria display optimal transport near surfaces -- bacteria as\n intermittent active chiral particles: trapped by hydrodynamics, escaping by\n adhesion: The near-surface swimming patterns of bacteria are strongly determined by the\nhydrodynamic interactions between bacteria and the surface, which trap bacteria\nin smooth circular trajectories that lead to inefficient surface exploration.\nHere, we show by combining experiments and a data-driven mathematical model\nthat surface exploration of enterohemorrhagic Escherichia coli (EHEC) -- a\npathogenic strain of E. coli causing serious illnesses such as bloody diarrhea\n-- results from a complex interplay between motility and transient surface\nadhesion events. These events allow EHEC to break the smooth circular\ntrajectories and regulate their transport properties by the use stop-adhesion\nevents that lead to a characteristic intermittent motion on surfaces. We find\nthat the experimentally measured frequency of stop-adhesion events in EHEC is\nlocated at the value predicted by the developed mathematical model that\nmaximizes bacterial surface diffusivity. We indicate that these results and the\ndeveloped model apply to other bacterial strains on different surfaces, which\nsuggests that swimming bacteria use transient adhesion to regulate surface\nmotion.", "category": "physics_bio-ph" }, { "text": "Estimation of Possible Selectivity and Sensitivity of a Cooperative\n System to Low-Intensive Microwave Radiation: Recently, origins of non-deterministic behavior and free will in living\nsystems obtain growing interest (see, e.g. Maye A, Hsieh C, Sugihara G, Brembs\nB (2007) Order in Spontaneous Behavior. PLoS ONE 2(5): e443.\ndoi:10.1371/journal.pone.0000443). In this text, devoted to electromagnetic\nhypersensitivity, in n.2 and n.4, a possible physical mechanism of free will\nand consequent indeterminacy in behavior is discussed.", "category": "physics_bio-ph" }, { "text": "La luz que perciben las abejas: This project delves into the concepts of electromagnetic waves of light and\nintroduces the concepts of wavelength and polarization, these concepts are\nrelated to the ability of bees to perceive ultraviolet light and polarized\nlight. This causal chain of physical phenomena is studied through a detailed\ndescription of light sources and the ways in which it can be polarized in the\nenvironment in which bees live. In addition, the anatomical mechanisms in which\nthe perception of bees is possible are studied. It is proposed that the\ndifferent types of light exposure studied are an important part in the\nexperience, interaction, communication and feeding of these insects.", "category": "physics_bio-ph" }, { "text": "Plasmonic Toroidal Metamolecules Assembled by DNA Origami: We demonstrate hierarchical assembly of plasmonic toroidal metamolecules,\nwhich exhibit tailored optical activity in the visible spectral range. Each\nmetamolecule consists of four identical origami-templated helical building\nblocks. Such toroidal metamolecules show stronger chiroptical response than\nmonomers and dimers of the helical building blocks. Enantiomers of the\nplasmonic structures yield opposite circular dichroism spectra. The\nexperimental results agree well with the theoretical simulations. We also\ndemonstrate that given the circular symmetry of the structures, distinct\nchiroptical response along their axial orientation can be uncovered via simple\nspin-coating of the metamolecules on substrates. Our work provides a new\nstrategy to create plasmonic chiral platforms with sophisticated nanoscale\narchitectures for potential applications such as chiral sensing using\nchemically-based assembly systems.", "category": "physics_bio-ph" }, { "text": "Dynamics of ions in the selectivity filter of the KcsA channel: Towards\n a coupled Brownian particle description: The statistical and dynamical properties of ions in the selectivity filter of\nthe KcsA ion channel are considered on the basis of molecular dynamics (MD)\nsimulations of the KcsA protein embedded in a lipid membrane surrounded by an\nionic solution. A new approach to the derivation of a Brownian dynamics (BD)\nmodel of ion permeation through the filter is discussed, based on unbiased MD\nsimulations. It is shown that depending on additional assumptions, ion's\ndynamics can be described either by under-damped Langevin equation with\nconstant damping and white noise or by Langevin equation with a fractional\nmemory kernel. A comparison of the potential of the mean force derived from\nunbiased MD simulations with the potential produced by the umbrella sampling\nmethod demonstrates significant differences in these potentials. The origin of\nthese differences is an open question that requires further clarifications.", "category": "physics_bio-ph" }, { "text": "An energy landscape approach to locomotor transitions in complex 3D\n terrain: Effective locomotion in nature happens by transitioning across multiple modes\n(e.g., walk, run, climb). Despite this, far more mechanistic understanding of\nterrestrial locomotion has been on how to generate and stabilize around\nnear-steady-state movement in a single mode. We still know little about how\nlocomotor transitions emerge from physical interaction with complex terrain.\nConsequently, robots largely rely on geometric maps to avoid obstacles, not\ntraverse them. Recent studies revealed that locomotor transitions in complex\n3-D terrain occur probabilistically via multiple pathways. Here, we show that\nan energy landscape approach elucidates the underlying physical principles. We\ndiscovered that locomotor transitions of animals and robots self-propelled\nthrough complex 3-D terrain correspond to barrier-crossing transitions on a\npotential energy landscape. Locomotor modes are attracted to landscape basins\nseparated by potential energy barriers. Kinetic energy fluctuation from\noscillatory self-propulsion helps the system stochastically escape from one\nbasin and reach another to make transitions. Escape is more likely towards\nlower barrier direction. These principles are surprisingly similar to those of\nnear-equilibrium, microscopic systems. Analogous to free energy landscapes for\nmulti-pathway protein folding transitions, our energy landscape approach from\nfirst principles is the beginning of a statistical physics theory of\nmulti-pathway locomotor transitions in complex terrain. This will not only help\nunderstand how the organization of animal behavior emerges from multi-scale\ninteractions between their neural and mechanical systems and the physical\nenvironment, but also guide robot design, control, and planning over the large,\nintractable locomotor-terrain parameter space to generate robust locomotor\ntransitions through the real world.", "category": "physics_bio-ph" }, { "text": "Spatially Heterogeneous Dynamics of Cells in a Growing Tumor Spheroid:\n Comparison Between Theory and Experiments: Collective cell movement, characterized by multiple cells that are in contact\nfor substantial periods of time and undergo correlated motion, plays a central\nrole in cancer and embryogenesis. Recent imaging experiments have provided\ntime-dependent traces of individual cells, thus providing an unprecedented\npicture of tumor spheroid growth. By using simulations of a minimal cell model,\nwe analyze the experimental data that map the movement of cells in fibrosarcoma\ntumor spheroid embedded in a collagen matrix. Both simulations and experiments\nshow that cells in the core of the spheroid exhibit subdiffusive glassy\ndynamics (mean square displacement, $\\Delta(t) \\approx t^{\\alpha}$ with $\\alpha\n< 1$), whereas cells in the periphery exhibit superdiffusive motion, $\\Delta(t)\n\\approx t^{\\alpha}$ with $\\alpha>1)$. The motion of most of the cells near the\nperiphery undergo highly persistent and correlated directional motion, thus\nexplaining the observed superdiffusive behavior. The $\\alpha$ values for cells\nin the core and periphery, extracted from simulations and experiments are in\nnear quantitative agreement with each other, which is surprising given that no\nparameter in the model was used to fit the measurements. The qualitatively\ndifferent dynamics of cells in the core and periphery is captured by the fourth\norder susceptibility, introduced to characterize metastable states in glass\nforming systems. Analyses of the velocity autocorrelation of individual cells\nshow remarkable spatial heterogeneity with no two cells exhibiting similar\nbehavior. The prediction that $\\alpha$ should depend on the location of the\ncells in the tumor is amenable to experimental test. The highly heterogeneous\ndynamics of cells in the tumor spheroid provides a plausible mechanism for the\norigin of intratumor heterogeneity.", "category": "physics_bio-ph" }, { "text": "Elastic Model for Dinucleosome Structure and Energy: The equilibrium structure of a Dinucleosome is studied using an elastic model\nthat takes into account the force and torque balance conditions. Using the\nproper boundary conditions, it is found that the conformational energy of the\nproblem does not depend on the length of the linker DNA. In addition it is\nshown that the two histone octamers are almost perpendicular to each other and\nthe linker DNA in short lengths is almost straight. These findings could shed\nsome light on the role of DNA elasticity in the chromatin structure.", "category": "physics_bio-ph" }, { "text": "Autoregulation of the total number of cells in culture: According to the universally accepted concept of the development of life on\nthe Earth, multicellular organisms initially emerged as a result of either the\nunion of identical unicellular organisms with the following functional\ndifferentiation, or the union of symbionts, in which there already was a\ncertain simple functional separation. However, in either case the progenitors\nof multicellular organisms were ensembles, communities of unicellular\norganisms. For a certain number of unicellular organisms to be treated as an\nensemble, there must be some interconnection between its members. Colonies of\nmechanically connected unicellular organisms were a later, more advanced stage;\nhere, unicellular organisms living separately are considered. Such\ninterconnection must, in particular, limit from above the total numbers of the\nmembers of the ensemble, because an excessive increase in these numbers could\ndisturb the connections between members of the ensemble to the extent of its\ndestruction. In addition, too large numbers of members in the ensemble could\nlead to nutrient depletion in its habitat. One can assume that such\ninterconnection between unicellular organisms was evolutionarily developed and\ngenetically fixed. I assumed that modern unicellular organisms retain such an\nability to regulate their total numbers. The validity of this assumption was\ntested in experiments, whose results are presented in this paper.", "category": "physics_bio-ph" }, { "text": "Activity driven fluctuations in living cells: We propose a model for the dynamics of a probe embedded in a living cell,\nwhere both thermal fluctuations and nonequilibrium activity coexist. The model\nis based on a confining harmonic potential describing the elastic cytoskeletal\nmatrix, which undergoes random active hops as a result of the nonequilibrium\nrearrangements within the cell. We describe the probe's statistics and we bring\nforth quantities affected by the nonequilibrium activity. We find an excellent\nagreement between the predictions of our model and experimental results for\ntracers inside living cells. Finally, we exploit our model to arrive at\nquantitative predictions for the parameters characterizing nonequilibrium\nactivity, such as the typical time scale of the activity and the amplitude of\nthe active fluctuations.", "category": "physics_bio-ph" }, { "text": "The Surface Laplacian Technique in EEG: Theory and Methods: This paper reviews the method of surface Laplacian differentiation to study\nEEG. We focus on topics that are helpful for a clear understanding of the\nunderlying concepts and its efficient implementation, which is especially\nimportant for EEG researchers unfamiliar with the technique. The popular\nmethods of finite difference and splines are reviewed in detail. The former has\nthe advantage of simplicity and low computational cost, but its estimates are\nprone to a variety of errors due to discretization. The latter eliminates all\nissues related to discretization and incorporates a regularization mechanism to\nreduce spatial noise, but at the cost of increasing mathematical and\ncomputational complexity. These and several others issues deserving further\ndevelopment are highlighted, some of which we address to the extent possible.\nHere we develop a set of discrete approximations for Laplacian estimates at\nperipheral electrodes and a possible solution to the problem of multiple-frame\nregularization. We also provide the mathematical details of finite difference\napproximations that are missing in the literature, and discuss the problem of\ncomputational performance, which is particularly important in the context of\nEEG splines where data sets can be very large. Along this line, the matrix\nrepresentation of the surface Laplacian operator is carefully discussed and\nsome figures are given illustrating the advantages of this approach. In the\nfinal remarks, we briefly sketch a possible way to incorporate finite-size\nelectrodes into Laplacian estimates that could guide further developments.", "category": "physics_bio-ph" }, { "text": "Mechanics of torque generation in the bacterial flagellar motor: The bacterial flagellar motor (BFM) is responsible for driving bacterial\nlocomotion and chemotaxis, fundamental processes in pathogenesis and biofilm\nformation. In the BFM, torque is generated at the interface between\ntransmembrane proteins (stators) and a rotor. It is well-established that the\npassage of ions down a transmembrane gradient through the stator complex\nprovides the energy needed for torque generation. However, the physics involved\nin this energy conversion remain poorly understood. Here we propose a\nmechanically specific model for torque generation in the BFM. In particular, we\nidentify two fundamental forces involved in torque generation: electrostatic\nand steric. We propose that electrostatic forces serve to position the stator,\nwhile steric forces comprise the actual 'power stroke'. Specifically, we\npredict that ion-induced conformational changes about a proline 'hinge' residue\nin an $\\alpha$-helix of the stator are directly responsible for generating the\npower stroke. Our model predictions fit well with recent experiments on a\nsingle-stator motor. Furthermore, we propose several experiments to elucidate\nthe torque-speed relationship in motors where the number of stators may not be\nconstant. The proposed model provides a mechanical explanation for several\nfundamental features of the flagellar motor, including: torque-speed and\nspeed-ion motive force relationships, backstepping, variation in step sizes,\nand the puzzle of swarming experiments.", "category": "physics_bio-ph" }, { "text": "Mechanical oscillations at the cellular scale: Active phenomena which involve force generation and motion play a key role in\na number of phenomena in living cells such as cell motility, muscle contraction\nand the active transport of material and organelles. Here we discuss mechanical\noscillations generated by active systems in cells. Examples are oscillatory\nregimes in muscles, the periodic beating of axonemal cilia and flagella and\nspontaneous oscillations of auditory hair cells which play a role in active\namplification of weak sounds in hearing. As a prototype system for oscillation\ngeneration by proteins, we discuss a general mechanism by which many coupled\nactive elements such as motor molecules can generate oscillations.", "category": "physics_bio-ph" }, { "text": "Crowding and pausing strongly affect dynamics of kinesin-1 motors along\n microtubules: Molecular motors of the kinesin-1 family move in a directed and processive\nfashion along microtubules (MTs). It is generally accepted that steric\nhindrance of motors leads to crowding effects; however, little is known about\nthe specific interactions involved. We employ an agent-based lattice gas model\nto study the impact of interactions which enhance the detachment of motors from\ncrowded filaments on their collective dynamics. The predictions of our model\nquantitatively agree with the experimentally observed concentration dependence\nof key motor characteristics including their run length, dwell time, velocity,\nand landing rate. From the anomalous stepping statistics of individual motors\nwhich exhibit relatively long pauses we infer that kinesin-1 motors sometimes\nlapse into an inactive state. Hereby, the formation of traffic jams amplifies\nthe impact of single inactive motors and leads to a crowding dependence of the\nfrequencies and durations of the resulting periods of no or slow motion. We\ninterpret these findings and conclude that kinesin-1 spends a significant\nfraction of its stepping cycle in a weakly bound state in which only one of its\nheads is bound to the MT.", "category": "physics_bio-ph" }, { "text": "Rigidity-induced scale invariance in polymer ejection from capsid: While the dynamics of a fully flexible polymer ejecting a capsid through a\nnanopore has been extensively studied, the ejection dynamics of semiflexible\npolymers has not been properly characterized. Here we report results from\nsimulations of ejection dynamics of semiflexible polymers ejecting from\nspherical capsids. Ejections start from strongly confined polymer conformations\nof constant initial monomer density. We find that, unlike for fully flexible\npolymers, for semiflexible polymers the force measured at the pore does not\nshow a direct relation to the instantaneous ejection velocity. The cumulative\nwaiting time $t(s)$, that is, the time at which a monomer $s$ exits the capsid\nthe last time, shows a clear change when increasing the polymer rigidity\n$\\kappa$. Major part of an ejecting polymer is driven out of the capsid by\ninternal pressure. At the final stage the polymer escapes the capsid by\ndiffusion. For the driven part there is a cross-over from essentially\nexponential growth of $t$ with $s$ of the fully flexible polymers to a\nscale-invariant form. In addition, a clear dependence of $t$ on $N_0$ was\nfound. These findings combined give the dependence $t(s) \\propto N_0^{0.55}\ns^{1.33}$ for the strongly rigid polymers. This cross-over in dynamics where\n$\\kappa$ acts as a control parameter is reminiscent of a phase transition. This\nanalogy is further enhanced by our finding a perfect data collapse of $t$ for\npolymers of different $N_0$ and any constant $\\kappa$.", "category": "physics_bio-ph" }, { "text": "Mapping robust multiscale communities in chromosome contact networks: To better understand DNA's 3D folding in cell nuclei, researchers developed\nchromosome capture methods such as Hi-C that measure the contact frequencies\nbetween all DNA segment pairs across the genome. As Hi-C data sets often are\nmassive, it is common to use bioinformatics methods to group DNA segments into\n3D regions with correlated contact patterns, such as Topologically Associated\nDomains (TADs) and A/B compartments. Recently, another research direction\nemerged that treats the Hi-C data as a network of 3D contacts. In this\nrepresentation, one can use community detection algorithms from complex network\ntheory that group nodes into tightly connected mesoscale communities. However,\nbecause Hi-C networks are so densely connected, several node partitions may\nrepresent feasible solutions to the community detection problem but are\nindistinguishable unless including other data. Because this limitation is a\nfundamental property of the network, this problem persists regardless of the\ncommunity-finding or data-clustering method. To help remedy this problem, we\ndeveloped a method that charts the solution landscape of network partitions in\nHi-C data from human cells. Our approach allows us to scan seamlessly through\nthe scales of the network and determine regimes where we can expect reliable\ncommunity structures. We find that some scales are more robust than others and\nthat strong clusters may differ significantly. Our work highlights that finding\na robust community structure hinges on thoughtful algorithm design or method\ncross-evaluation.", "category": "physics_bio-ph" }, { "text": "A simplified drift-diffusion model for pandemic propagation: Predicting Pandemic evolution involves complex modeling challenges, often\nrequiring detailed discrete mathematics executed on large volumes of\nepidemiological data. Differential equations have the advantage of offering\nsmooth, well-behaved solutions that try to capture overall predictive trends\nand averages. We further simplify one of those equations, the SIR model, by\noffering quasi-analytical solutions and fitting functions that agree well with\nthe numerics, as well as COVID-19 data across a few countries. The equations\nprovide an elegant way to visualize the evolution, by mapping onto the dynamics\nof an overdamped classical particle moving in the SIR configuration space,\ndrifting down gradient of a potential whose shape is set by the model and\nparameters in hand. We discuss potential sources of errors in our analysis and\ntheir growth over time, and map those uncertainties into a diffusive jitter\nthat tends to push the particle away from its minimum. The combined physical\nunderstanding and analytical expressions offered by such an intuitive\ndrift-diffusion model could be particularly useful in making policy decisions\ngoing forward.", "category": "physics_bio-ph" }, { "text": "Negative differential thermal resistance induced by ballistic transport: Using nonequilibrium molecular-dynamics simulations, we study the temperature\ndependence of the negative differential thermal resistance that appears in\ntwo-segment Frenkel-Kontorova lattices. We apply the theoretical method based\non Landauer equation to obtain the relationship between the heat current and\nthe temperature, which states a fundamental interpretation about the underlying\nphysical mechanism of the negative differential thermal resistance. The\ntemperature profiles and transport coefficients are demonstrated to explain the\ncrossover from diffusive to ballistic transport. The finite-size effect is also\ndiscussed.", "category": "physics_bio-ph" }, { "text": "Apex predator and the cyclic competition in a rock-paper-scissors game\n of three species: This work deals with the effects of an apex predator on the cyclic\ncompetition among three distinct species that follow the rules of the\nrock-paper-scissors game. The investigation develops standard stochastic\nsimulations but is motivated by a novel procedure which is explained in the\nwork. We add the apex predator as the fourth species in the system that\ncontains three species that evolve following the standard rules of migration,\nreproduction and predation, and study how the system evolves in this new\nenvironment, in comparison with the case in the absence of the apex predator.\nThe results show that the apex predator engenders the tendency to spread\nuniformly in the lattice, contributing to destroy the spiral patterns, keeping\nbiodiversity but diminishing the average size of the clusters of the species\nthat compete cyclically.", "category": "physics_bio-ph" }, { "text": "Are there optical communication channels in the brain?: Despite great progress in neuroscience, there are still fundamental\nunanswered questions about the brain, including the origin of subjective\nexperience and consciousness. Some answers might rely on new physical\nmechanisms. Given that biophotons have been discovered in the brain, it is\ninteresting to explore if neurons use photonic communication in addition to the\nwell-studied electro-chemical signals. Such photonic communication in the brain\nwould require waveguides. Here we review recent work [S. Kumar, K. Boone, J.\nTuszynski, P. Barclay, and C. Simon, Scientific Reports 6, 36508 (2016)]\nsuggesting that myelinated axons could serve as photonic waveguides. The light\ntransmission in the myelinated axon was modeled, taking into account its\nrealistic imperfections, and experiments were proposed both in-vivo and\nin-vitro to test this hypothesis. Potential implications for quantum biology\nare discussed.", "category": "physics_bio-ph" }, { "text": "The effect of electric fields on lipid membranes: Contrary to existing theoretical models, experimental evidence points out\nthat electroporation (membrane defect formation under external electric fields)\nstarts to occur within the range of transmembrane voltages that cells may\nroutinely experience, curiously, just above the range of transmembrane voltages\ninvolved in neural signal transmission. Understanding the underlying principles\nof electric fields-lipid membrane interactions seems to carry a great\nbiological importance.\n An argument is presented toward understanding the theoretical aspects of\nelectroporation by using the DLVO theory, which has not been recognized\npreviously in the context of electroporation. Further, the dispersion\ninteractions (with its quantum nature), of the double layer counterions and\nmembrane lipid molecules over the Stern layer are emphasized. The sign of these\nforces is such that they compress the membrane. A parallel is drawn to the\ntheory of thin films. The argument is that the external electric field breaks\nthe symmetry of the disjoining pressures on both sides of a lipid membrane,\nresulting in a protrusion of only few lipid molecules. That compromises the\nmembrane stability on a nanoscale and makes it traversable to ions. The\npresented estimate based on these arguments is consistent to electroporation\nexperiments and existing numerical simulations.", "category": "physics_bio-ph" }, { "text": "Non-equilibrium, stochastic model for tRNA binding time statistics: Protein translation is one of the most important processes in cell life but,\ndespite being well understood biochemically, the implications of its intrinsic\nstochastic nature have not been fully elucidated. In this paper we develop a\nmicroscopic and stochastic model which describes a crucial step in protein\ntranslation, namely the binding of the tRNA to the ribosome. Our model\nexplicitly takes into consideration tRNA recharging dynamics, spatial\ninhomogeneity and stochastic fluctuations in the number of charged tRNAs around\nthe ribosome. By analyzing this non-equilibrium system we are able to derive\nthe statistical distribution of the times needed by the tRNAs to bind to the\nribosome, and to show that it deviates from an exponential due to the coupling\nbetween the fluctuations of charged and uncharged populations of tRNA.", "category": "physics_bio-ph" }, { "text": "The Poisson ratio of the cellular actin cortex is frequency-dependent: Cell shape changes are vital for many physiological processes such as cell\nproliferation, cell migration and morphogenesis. They emerge from an\norchestrated interplay of active cellular force generation and passive cellular\nforce response - both crucially influenced by the actin cytoskeleton. To model\ncellular force response and deformation, cell mechanical models commonly\ndescribe the actin cytoskeleton as a contractile isotropic incompressible\nmaterial. However, in particular at slow frequencies, there is no compelling\nreason to assume incompressibility as the water content of the cytoskeleton may\nchange. Here we challenge the assumption of incompressibility by comparing\ncomputer simulations of an isotropic actin cortex with tunable Poisson ratio to\nmeasured cellular force response. Comparing simulation results and experimental\ndata, we determine the Poisson ratio of the cortex in a frequency-dependent\nmanner. We find that the Poisson ratio of the cortex decreases with frequency\nlikely due to actin cortex turnover leading to an over-proportional decrease of\nshear stiffness at larger time scales. We thus report a trend of the Poisson\nratio similar to that of glassy materials, where the frequency-dependence of\njamming leads to an analogous effect.", "category": "physics_bio-ph" }, { "text": "Phase synchronization in a sparse network of randomly connected neurons\n under the effect of Poissonian spike inputs: This article investigates the emergence of phase synchronization in a network\nof randomly connected neurons by chemical synapses. The study uses the classic\nHodgkin-Huxley model to simulate the neuronal dynamics under the action of a\ntrain of Poissonian spikes. In such a scenario, we observed the emergence of\nirregular spikes for a specific range of conductances, and also that the phase\nsynchronization of the neurons is reached when the external current is strong\nenough to induce spiking activity but without overcoming the coupling current.\nConversely, if the external current assumes very high values, then an opposite\neffect is observed, i.e. the prevention of the network synchronization. We\nexplain such behaviors considering different mechanisms involved in the system,\nsuch as incoherence, minimization of currents, and stochastic effects from the\nPoissonian spikes. Furthermore, we present some numerical simulations where the\nstimulation of only a fraction of neurons, for instance, can induce phase\nsynchronization in the non-stimulated fraction of the network, besides cases in\nwhich for larger coupling values it is possible to propagate the spiking\nactivity in the network when considering stimulation over only one neuron.", "category": "physics_bio-ph" }, { "text": "Signatures of heterogeneity in the statistical structure of target state\n aligned ensembles: Finite time convergence to functionally important target states is a key\ncomponent of many biological processes. We previously found that the terminal\napproach phase of such dynamics exhibits universal types of stochastic dynamics\nthat differ qualitatively between noise-dominated and force-dominated regimes\nof the approach dynamics. While for the noise-dominated regime the approach\ndynamics is uninformative about the underlying force law, in the\nforce-dominated regime it enables the accurate inference of the underlying\ndynamics. Biological systems often exhibit substantial parameter heterogeneity,\nfor instance through copy number fluctuations of key molecules or variability\nin modulating factors. Here, we extend our theory of target state aligned (TSA)\nstochastic dynamics to investigate the impact of parameter heterogeneity in the\nunderlying stochastic dynamics. We examine the approach to target states for a\nwide range of dynamical laws and additive as well as multiplicative noise. We\nfind that the distinct regimes of noise-dominated and force-dominated dynamics\nstrongly differ in their sensitivity to parameter heterogeneity. In the\nnoise-dominated regime, TSA ensembles are insensitive to parameter\nheterogeneity in the force law, but sensitive to sample to sample heterogeneity\nin the diffusion constant. For force-dominated dynamics, both parameter\nheterogeneity in the force law and diffusion constant change the behaviour of\nthe non-stationary statistics and in particular the two-time-covariance\nfunctions. In this regime, TSA ensembles provide a sensitive readout of\nparameter heterogeneity. Under natural conditions, parameter heterogeneity in\nmany biological systems cannot be experimentally controlled or eliminated. Our\nresults provide a systematic theoretical foundation for the analysis of target\nstate directed dynamics in a large class of systems with substantial\nheterogeneity.", "category": "physics_bio-ph" }, { "text": "Diffusion wave and signal transduction in biological live cells: Transduction of mechanical stimuli into biochemical signals is a fundamental\nsubject for cell physics. In the experiments of FRET signal in cells a wave\npropagation in nanoscope was observed. We here develop a diffusion wave concept\nand try to give an explanation to the experimental observation. The theoretical\nprediction is in good agreement to result of the experiment.", "category": "physics_bio-ph" }, { "text": "Solute transport within single pores post-pulse: We present results of studying the post-pulse transport properties of single\npores. Single pores exhibit active transport (drift), and not just passive\ntransport (diffusion) at early post-pulse times. In addition, we suggest\nexperimental design methods obtained from model parameters that would enable\nexperimentalists to find localized regions of a few pores.", "category": "physics_bio-ph" }, { "text": "Tribological Analysis of Ventral Scale Structure in a Python Regius in\n Relation to Laser Textured Surfaces: Laser Texturing is one of the leading technologies applied to modify surface\ntopography. To date, however, a standardized procedure to generate\ndeterministic textures is virtually non-existent. In nature, especially in\nsquamata, there are many examples of deterministic structured textures that\nallow species to control friction and condition their tribological response for\nefficient function. In this work, we draw a comparison between industrial\nsurfaces and reptilian surfaces. We chose the python regius species as a\nbio-analogue with a deterministic surface. We first study the structural make\nup of the ventral scales of the snake (both construction and metrology). We\nfurther compare the metrological features of the ventral scales to\nexperimentally recommended performance indicators of industrial surfaces\nextracted from open literature. The results indicate the feasibility of\nengineering a Laser Textured Surface based on the reptilian ornamentation\nconstructs. It is shown that the metrological features, key to efficient\nfunction of a rubbing deterministic surface, are already optimized in the\nreptile. We further show that optimization in reptilian surfaces is based on\nsynchronizing surface form, textures and aspects to condition the frictional\nresponse. Mimicking reptilian surfaces, we argue, may form a design methodology\npotentially capable of generating advanced deterministic surface constructs\ncapable of efficient tribological function.", "category": "physics_bio-ph" }, { "text": "Microscopic and macroscopic models for the onset and progression of\n Alzheimer's disease: In the first part of this paper we review a mathematical model for the onset\nand progression of Alzheimer's disease (AD) that was developed in subsequent\nsteps over several years. The model is meant to describe the evolution of AD in\nvivo. In [Y. Achdou et al., 2013] we treated the problem at a microscopic\nscale, where the typical length scale is a multiple of the size of the soma of\na single neuron. Subsequently, in [M. Bertsch at al., 2016] we concentrated on\nthe macroscopic scale, where brain neurons are regarded as a continuous medium,\nstructured by their degree of malfunctioning.\n In the second part of the paper we consider the relation between the\nmicroscopic and the macroscopic models. In particular we show under which\nassumptions the kinetic transport equation, which in the macroscopic model\ngoverns the evolution of the probability measure for the degree of\nmalfunctioning of neurons, can be derived from a particle-based setting.\n In the microscopic model we consider basically mechanism i), modelling it by\na system of Smoluchowski equations for the amyloid concentration (describing\nthe agglomeration phenomenon), with the addition of a diffusion term as well as\nof a source term on the neuronal membrane. At the macroscopic level instead we\nmodel processes i) and ii) by a system of Smoluchowski equations for the\namyloid concentration, coupled to a kinetic-type transport equation for the\ndistribution function of the degree of malfunctioning of the neurons. The\nsecond equation contains an integral term describing the random onset of the\ndisease as a jump process localized in particularly sensitive areas of the\nbrain.\n Even though we deliberately neglected many aspects of the complexity of the\nbrain and the disease, numerical simulations are in both cases (microscopic and\nmacroscopic) in good qualitative agreement with clinical data.", "category": "physics_bio-ph" }, { "text": "Optical Antenna-based Fluorescence Correlation Spectroscopy to Probe the\n Nanoscale Dynamics of Biological Membranes: The plasma membrane of living cells is compartmentalized at multiple spatial\nscales ranging from the nano- to the meso-scale. This non-random organization\nis crucial for a large number of cellular functions. At the nanoscale, cell\nmembranes organize into dynamic nano-assemblies enriched by cholesterol,\nsphingolipids and certain types of proteins. Investigating these\nnano-assemblies known as lipid rafts is of paramount interest in fundamental\ncell biology. However, this goal requires simultaneous nanometer spatial\nprecision and microsecond temporal resolution which is beyond the reach of\ncommon microscopes. Optical antennas based on metallic nanostructures\nefficiently enhance and confine light into nanometer dimensions, breaching the\ndiffraction limit of light. In this Perspective, we discuss recent progress\ncombining optical antennas with fluorescence correlation spectroscopy (FCS) to\nmonitor microsecond dynamics at nanoscale spatial dimensions. These new\ndevelopments offer numerous opportunities to investigate lipid and protein\ndynamics in both mimetic and native biological membranes.", "category": "physics_bio-ph" }, { "text": "Quantification of flux for non-equilibrium dynamics and thermodynamics\n for driving non-Michaelis-Menton Enzyme Rates: The driving force for active physical and biological systems is determined by\nboth the underlying landscape and the non-equilibrium curl flux. While\nlandscape can be quantified in the experiments by the histograms of the\ncollecting trajectories of the observables, the experimental flux\nquantification is still challenging. In this work, we studied the single\nmolecule enzyme dynamics and observed the deviation in kinetics from the\nconventional Michaelis-Menton reaction rate. We identified and quantified the\nnon-equilibrium flux as the origin of such non-Michaelis-Menton enzyme rate\nbehavior. This is the first time of rigorous quantification of the flux for the\ndriving force of the non-equilibrium active dynamics. We also quantified the\ncorresponding non-equilibrium thermodynamics in terms of chemical potential and\nentropy production. We identified and quantified the origin of the flux,\nchemical potential and entropy production as the heat absorbed (energy input)\nin the enzyme reaction.", "category": "physics_bio-ph" }, { "text": "Terminating spiral waves with a single designed stimulus: Teleportation\n as the mechanism for defibrillation: We demonstrate a universal mechanism for terminating spiral waves in\nexcitable media using an established topological framework. This mechanism\ndictates whether high- or low-energy defibrillation shocks succeed or fail.\nFurthermore, this mechanism allows for the design of a single minimal stimulus\ncapable of defibrillating, at any time, turbulent states driven by multiple\nspiral waves. We demonstrate this method in a variety of computational models\nof cardiac tissue ranging from simple to detailed human models. The theory\ndescribed here shows how this mechanism underlies all successful defibrillation\nand can be used to further develop existing and future low-energy\ndefibrillation strategies.", "category": "physics_bio-ph" }, { "text": "Challenging Eukaryogenesis: The Story of the Eukaryotic Ancestor: As the question of the origins of eukaryotes comes closer to an answer, the\ninteractions between the archaeal ancestor to eukaryotes and environmental,\nmolecular, bacterial, other influences and symbionts have become increasingly\nrelevant. Various studies have pointed towards the Lokiarchaeota as a close\narchaeal relative to the eukarya. A study by Imachi et al., published in early\n2020, was able to decipher the proteome and genome of the Loki and reported an\nentirely new model for eukaryogenesis due to its findings, thus shifting\nresearch of eukaryogenesis away from models focusing on endocytosis and the\nrapid acquisition of the alphaproteobacteria that would become the\nmitochondria. Imachi and colleagues proposed that ancestors of the Loki lived\nsymbiotically with other prokaryotes due to its shape, and facilitated\nmolecular transfer between the symbionts as well as the membrane manipulation\nnecessary to allow such transfer, before acquiring a proto-mitochondria over\ntime. This paper will lay out the history of endosymbiosis and the prevailing\ntheory of endocytosis between archaea and alphaproteobacteria, and consolidates\nthe knowns and unknowns up to before the publication of Imachi et al. The\nfindings of their novel study will be discussed, and the knowns and unknowns\nwith respect to these new findings are re-consolidated. The two models of\neukaryogenesis are compared and, in moving forward with Imachi and colleagues\nmodel, probable areas of research to further validate this approach are\ndiscussed, as well as potential usage of research tools of other fields to\nanswer the persistent unknowns of how eukaryotes came to be.", "category": "physics_bio-ph" }, { "text": "Distinguishing the roles of energy funnelling and delocalization in\n photosynthetic light harvesting: Photosynthetic complexes improve the transfer of excitation energy from\nperipheral antennas to reaction centers in several ways. In particular, a\ndownward energy funnel can direct excitons in the right direction, while\ncoherent excitonic delocalization can enhance transfer rates through the\ncooperative phenomenon of supertransfer. However, isolating the role of purely\ncoherent effects is difficult because any change to the delocalization also\nchanges the energy landscape. Here, we show that the relative importance of the\ntwo processes can be determined by comparing the natural light-harvesting\napparatus with counterfactual models in which the delocalization and the energy\nlandscape are altered. Applied to the example of purple bacteria, our approach\nshows that although supertransfer does enhance the rates somewhat, the\nenergetic funnelling plays the decisive role. Because delocalization has a\nminor role (and is sometimes detrimental), it is most likely not adaptive,\nbeing a side-effect of the dense chlorophyll packing that evolved to increase\nlight absorption per reaction center.", "category": "physics_bio-ph" }, { "text": "Autonomous free-energy transducer working under thermal fluctuations: By a modular combination of mesoscopic detectors and gates, we present a\nthoughtful pump that transports gas particles against the difference of their\ndensity at the expense of the diffusion of another species of gas particles. We\nalso discuss briefly the relevance of the model to the study of\nstructure-function relationship of the biomolecular machines.", "category": "physics_bio-ph" }, { "text": "A Null-model Exhibiting Synchronized Dynamics in Uncoupled Oscillators: The phenomenon of phase synchronization of oscillatory systems arising out of\nfeedback coupling is ubiquitous across physics and biology. In noisy, complex\nsystems, one generally observes transient epochs of synchronization followed by\nnon-synchronous dynamics. How does one guarantee that the observed transient\nepochs of synchronization are arising from an underlying feedback mechanism and\nnot from some peculiar statistical properties of the system? This question is\nparticularly important for complex biological systems where the search for a\nnon-existent feedback mechanism may turn out be an enormous waste of resources.\nIn this article, we propose a null model for synchronization motivated by\nexpectations on the dynamical behaviour of biological systems to provide a\nquantitative measure of the confidence with which one can infer the existence\nof a feedback mechanism based on observation of transient synchronized\nbehaviour. We demonstrate the application of our null model to the phenomenon\nof gait synchronization in free-swimming nematodes, C. elegans.", "category": "physics_bio-ph" }, { "text": "A general two-cycle network model of molecular motors: Molecular motors are single macromolecules that generate forces at the\npiconewton range and nanometer scale. They convert chemical energy into\nmechanical work by moving along filamentous structures. In this paper, we study\nthe velocity of two-head molecular motors in the framework of a mechanochemical\nnetwork theory. The network model, a generalization of the recently work of\nLiepelt and Lipowsky (PRL 98, 258102 (2007)), is based on the discrete\nmechanochemical states of a molecular motor with multiple cycles. By\ngeneralizing the mathematical method developed by Fisher and Kolomeisky for\nsingle cycle motor (PNAS(2001) 98(14) P7748-7753), we are able to obtain an\nexplicit formula for the velocity of a molecular motor.", "category": "physics_bio-ph" }, { "text": "Magnetic isotope effects: a potential testing ground for quantum biology: One possible explanation for magnetosensing in biology, such as avian\nmagnetoreception, is based on the spin dynamics of certain chemical reactions\nthat involve radical pairs. Radical pairs have been suggested to also play a\nrole in anesthesia, hyperactivity, neurogenesis, circadian clock rhythm,\nmicrotubule assembly, etc. It thus seems critical to probe the credibility of\nsuch models. One way to do so is through isotope effects with different nuclear\nspins. Here we briefly review the papers involving spin-related isotope effects\nin biology. We suggest studying isotope effects can be an interesting avenue\nfor quantum biology.", "category": "physics_bio-ph" }, { "text": "Conformational changes in glycine tri- and hexapeptide: We have investigated the potential energy surfaces for glycine chains\nconsisting of three and six amino acids. For these molecules we have calculated\npotential energy surfaces as a function of the Ramachandran angles phi and psi,\nwhich are widely used for the characterization of the polypeptide chains. These\nparticular degrees of freedom are essential for the characterization of\nproteins folding process. Calculations have been carried out within ab initio\ntheoretical framework based on the density functional theory and accounting for\nall the electrons in the system. We have determined stable conformations and\ncalculated the energy barriers for transitions between them. Using a\nthermodynamic approach, we have estimated the times of the characteristic\ntransitions between these conformations. The results of our calculations have\nbeen compared with those obtained by other theoretical methods and with the\navailable experimental data extracted from the Protein Data Base. This\ncomparison demonstrates a reasonable correspondence of the most prominent\nminima on the calculated potential energy surfaces to the experimentally\nmeasured angles phi and psi for the glycine chains appearing in native\nproteins. We have also investigated the influence of the secondary structure of\npolypeptide chains on the formation of the potential energy landscape. This\nanalysis has been performed for the sheet and the helix conformations of chains\nof six amino acids.", "category": "physics_bio-ph" }, { "text": "Cluster Analysis of Gene Expression Data: The expression levels of many thousands of genes can be measured\nsimultaneously by DNA microarrays (chips). This novel experimental tool has\nrevolutionized research in molecular biology and generated considerable\nexcitement. A typical experiment uses a few tens of such chips, each dedicated\nto a single sample - such as tissue extracted from a particular tumor. The\nresults of such an experiment contain several hundred thousand numbers, that\ncome in the form of a table, of several thousand rows (one for each gene) and\n50 - 100 columns (one for each sample). We developed a clustering methodology\nto mine such data. In this review I provide a very basic introduction to the\nsubject, aimed at a physics audience with no prior knowledge of either gene\nexpression or clustering methods. I explain what genes are, what is gene\nexpression and how it is measured by DNA chips. Next I explain what is meant by\n\"clustering\" and how we analyze the massive amounts of data from such\nexperiments, and present results obtained from analysis of data obtained from\ncolon cancer, brain tumors and breast cancer.", "category": "physics_bio-ph" }, { "text": "Inferring geometrical dynamics of cell nucleus translocation: The ability of eukaryotic cells to squeeze through constrictions is limited\nby the stiffness of their large and rigid nucleus. However, migrating cells are\noften able to overcome this limitation and pass through constrictions much\nsmaller than their nucleus, a mechanism that is not yet understood. This is\nwhat we address here through a data-driven approach using microfluidic devices\nwhere cells migrate through controlled narrow spaces of sizes comparable to the\nones encountered in physiological situations. Stochastic Force Inference is\napplied to experimental nuclear trajectories and nuclear shape descriptors,\nresulting in equations that effectively describe this phenomenon of nuclear\ntranslocation. By employing a model where the channel geometry is an explicit\nparameter and by training it over experimental data with different sizes of\nconstrictions, we ensure that the resulting equations are predictive to other\ngeometries. Altogether, the approach developed here paves the way for a\nmechanistic and quantitative description of dynamical cell complexity during\nits motility.", "category": "physics_bio-ph" }, { "text": "ATR-FTIR spectroscopy detects alterations induced by organotin(IV)\n carboxylates in MCF-7 cells at sub-cytotoxic/-genotoxic concentrations: The environmental impact of metal complexes such as organotin(IV) compounds\nis of increasing concern. Genotoxic effects of organotin(IV) compounds (0.01\nmicrog/ml, 0.1 microg/ml or 1.0 microg/ml) were measured using the alkaline\nsingle-cell gel electrophoresis (comet) assay to measure DNA single-strand\nbreaks (SSBs) and the cytokinesis-block micronucleus (CBMN) assay to determine\nmicronucleus formation. Biochemical-cell signatures were also ascertained using\nattenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy.\nIn the comet assay, organotin(IV) carboxylates induced significantly-elevated\nlevels of DNA SSBs. Elevated micronucleus-forming activities were also\nobserved. Following interrogation using ATR-FTIR spectroscopy, infrared spectra\nin the biomolecular range (900 cm-1 - 1800 cm-1) derived from orga...", "category": "physics_bio-ph" }, { "text": "Thermo-mechanic-electrical coupling in phospholipid monolayers near the\n critical point: Lipid monolayers have been shown to represent a powerful tool in studying\nmechanical and thermodynamic properties of lipid membranes as well as their\ninteraction with proteins. Using Einstein's theory of fluctuations we here\ndemonstrate, that an experimentally derived linear relationship both between\ntransition entropy S and area A as well as between transition entropy and\ncharge q implies a linear relationships between compressibility \\kappa_T, heat\ncapacity c_\\pi, thermal expansion coefficient \\alpha_T and electric capacity\nCT. We demonstrate that these couplings have strong predictive power as they\nallow calculating electrical and thermal properties from mechanical\nmeasurements. The precision of the prediction increases as the critical point\nTC is approached.", "category": "physics_bio-ph" }, { "text": "A simple atomistic model for the simulation of the gel phase of lipid\n bilayers: In this paper we present the results of a large-scale numerical investigation\nof structural properties of a model of cell membrane, simulated as a bilayer of\nflexible molecules in vacuum. The study was performed by carrying out extensive\nMolecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two\nsystems of different sizes (2x32 and 2x256 molecules), over a fairly large set\nof temperatures and densities, using parallel platforms and more standard\nserial computers. Depending on the dimension of the system, the dynamics was\nfollowed for physical times that go from few hundred of picoseconds for the\nlargest system to 5--10 nanoseconds for the smallest one. We find that the\nbilayer remains stable even in the absence of water and neglecting Coulomb\ninteractions in the whole range of temperatures and densities we have\ninvestigated. The extension of the region of physical parameters that we have\nexplored has allowed us to study significant points in the phase diagram of the\nbilayer and to expose marked structural changes as density and temperature are\nvaried, which are interpreted as the system passing from a crystal to a gel\nphase.", "category": "physics_bio-ph" }, { "text": "High Accuracy Protein Identification: Fusion of solid-state nanopore\n sensing and machine learning: Proteins are arguably the most important class of biomarkers for health\ndiagnostic purposes. Label-free solid-state nanopore sensing is a versatile\ntechnique for sensing and analysing biomolecules such as proteins at\nsingle-molecule level. While molecular-level information on size, shape, and\ncharge of proteins can be assessed by nanopores, the identification of proteins\nwith comparable sizes remains a challenge. Here, we present methods that\ncombine solid-state nanopore sensing with machine learning to address this\nchallenge. We assess the translocations of four similarly sized proteins using\namplifiers with bandwidths (BWs) of 100 kHz (sampling rate=200 ksps) and 10 MHz\n(sampling rate=40 Msps), the highest bandwidth reported for protein sensing,\nusing nanopores fabricated in <10 nm thick silicon nitride membranes. F-values\nof up to 65.9% and 83.2% (without clustering of the protein signals) were\nachieved with 100 kHz and 10 MHz BW instruments, respectively, for\nidentification of the four proteins. The accuracy of protein identification was\nsignificantly improved by grouping the signals into several clusters depending\non the event features, resulting in F-value and specificity reaching as high as\n88.7% and 96.4%, respectively, for combinations of four proteins. The combined\nimprovement in sensor signals through the use of high bandwidth instruments,\nadvanced clustering, machine learning, and other advanced data analysis methods\nallows identification of proteins with high accuracy.", "category": "physics_bio-ph" }, { "text": "Resolving controversy of unusually high refractive index of tubulin: Refractive index of tubulin is an important parameter underlying fundamental\nelectromagnetic and biophysical properties of microtubules - protein fibers\nessential for several cell functions including cell division. Yet, the only\nexperimental data available in the current literature show values of tubulin\nrefractive index (n\\,=\\,2.36\\,-\\,2.90) which are much higher than established\ntheories predict based on the weighted contribution of the polarizability of\nindividual amino acids constituting the protein. To resolve this controversy,\nwe report here modeling and rigorous experimental analysis of refractive index\nof purified tubulin dimer. Our experimental data revealed that the refractive\nindex of tubulin is n\\,=\\,1.64 at the wavelength 589\\,nm and 25\\,$^{\\circ}{\\rm\nC}$, that is much closer to the values predicted by established theories than\nthe earlier experimental data provide.", "category": "physics_bio-ph" }, { "text": "Dual critality of single-file transport through DNA channel: This paper has been withdrawn by authors due to publication requirement.", "category": "physics_bio-ph" }, { "text": "Universal constraint on nonlinear population dynamics: Ecological and evolutionary processes show various population dynamics\ndepending on internal interactions and environmental changes. While crucial in\npredicting biological processes, discovering general relations for such\nnonlinear dynamics has remained a challenge. Here, we derive a universal\ninformation-theoretical constraint on a broad class of nonlinear dynamical\nsystems represented as population dynamics. The constraint is interpreted as a\ngeneralization of Fisher's fundamental theorem of natural selection.\nFurthermore, the constraint indicates nontrivial bounds for the speed of\ncritical relaxation around bifurcation points, which we argue are universally\ndetermined only by the type of bifurcation. Our theory is verified for an\nevolutionary model and an epidemiological model, which exhibit the\ntranscritical bifurcation, as well as for an ecological model, which undergoes\nlimit-cycle oscillation. This work paves a way to predict biological dynamics\nin light of information theory, by providing fundamental relations in\nnonequilibrium statistical mechanics of nonlinear systems.", "category": "physics_bio-ph" }, { "text": "Dynamic Force Measurements on Swimming Chlamydomonas Cells using\n Micropipette Force Sensors: Flagella and cilia are cellular appendages that inherit essential functions\nof microbial life including sensing and navigating the environment. In order to\npropel a swimming microorganism they displace the surrounding fluid by means of\nperiodic motions, while precisely-timed modulations of their beating patterns\nenable the cell to steer towards or away from specific locations.\nCharacterizing the dynamic forces, however, is challenging and typically relies\non indirect experimental approaches. Here, we present direct in vivo\nmeasurements of the dynamic forces of motile Chlamydomonas reinhardtii cells in\ncontrolled environments. The experiments are based on partially aspirating a\nliving microorganism at the tip of a micropipette force sensor and optically\nrecording the micropipette's position fluctuations with high temporal and\nsub-pixel spatial resolution. We provide an analytic elasto-hydrodynamic model\nfor the micropipette force sensor and describe how to obtain the micropipette's\nfull frequency response function from a dynamic force calibration. Using this\napproach, we find dynamic forces during the free swimming activity of\nindividual Chlamydomonas reinhardtii cells of 23$\\pm$5 pN resulting from the\ncoordinated flagellar beating with a frequency of 51$\\pm$6 Hz. In addition to\nmeasurements in bulk liquid environment, we study the dynamic forces of the\nbiflagellated microswimmer in the vicinity of a solid/liquid interface. As we\ngradually decrease the distance of the swimming microbe to the interface, we\nmeasure a significantly enhanced force transduction at distances larger than\nthe maximum extend of the beating flagella, highlighting the importance of\nhydrodynamic interactions for scenarios in which flagellated microorganisms\nencounter surfaces.", "category": "physics_bio-ph" }, { "text": "Coherence and stochastic resonances in a noisy van der Pol-type\n circadian pacemaker model driven by light: Daylight plays a major role in the wake/sleep cycle in humans. Indeed, the\nwake/sleep system stems from biological systems that follow a circadian rhythm\ndetermined by the light/dark alternation. The oscillations can be modeled by\nthe higher order non-linearity van der Pol -type equation driven by a term that\nmimics the light cycle. In this work noise in the illumination is introduced to\ninvestigate its effect on the human circadian cycle. It is found that the\npresence of noise is detrimental for the sleep/wake rhythm, except for some\nspecial values for which it may favor regular oscillations. Depending for\nsystem parameters, noise induces regularities, such as stochastic resonance: if\nthe natural light is turned off, it emerges that there is an optimal value of\nintensity noise which most deteriorates the regularity of the cycle, it is the\nphenomenon of anti-coherent resonance. Also, the phenomenon of stochastic\nresonance occurs: in the presence of the drive of natural light, there is an\noptimal noise intensity which improves the evolution of the wake / sleep\nsystem. However, there is a critical value of the noise beyond which the system\nbecomes chaotic; indeed, for sufficiently high noise levels (how high depends\nupon the parameter of the system), the sleep/wake cycle evolves in a random and\nunpredictable manner, for whatever parameters of the external light.", "category": "physics_bio-ph" }, { "text": "Method for the Monte Carlo based Simulation of Lipid-Monolayers\n including Lipid Movement: A two-state-model consisting of hexagonally connected lipids being either in\nthe ordered or disordered state is used to set up a Monte Carlo Simulation for\nlipid monolayers. The connection of the lipids is realized by Newtonian springs\nemulating the surfaces elasticity and allowing for the calculation of\ntranslational movement of the lipids, whereas all necessary simulation\nparameters follow from experiments. Simulated monolayer isotherms can be\ndirectly compared to measured ones concurrently allowing the calculation of the\nexperimentally hardly accessible monolayer heat capacity.", "category": "physics_bio-ph" }, { "text": "Mechanical Instabilities of Biological Tubes: We study theoretically the shapes of biological tubes affected by various\npathologies. When epithelial cells grow at an uncontrolled rate, the negative\ntension produced by their division provokes a buckling instability. Several\nshapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all\nof which are found in pathologies of tracheal, renal tubes or arteries. The\nfinal shape depends crucially on the mechanical parameters of the tissues :\nYoung modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since\ntissues must be in quasistatic mechanical equilibrium, abnormal shapes convey\ninformation as to what causes the pathology. We calculate a phase diagram of\ntubular instabilities which could be a helpful guide for investigating the\nunderlying genetic regulation.", "category": "physics_bio-ph" }, { "text": "Mapping the conformations of biological assemblies: Mapping conformational heterogeneity of macromolecules presents a formidable\nchallenge to X-ray crystallography and cryo-electron microscopy, which often\npresume its absence. This has severely limited our knowledge of the\nconformations assumed by biological systems and their role in biological\nfunction, even though they are known to be important. We propose a new approach\nto determining to high resolution the three-dimensional conformations of\nbiological entities such as molecules, macromolecular assemblies, and\nultimately cells, with existing and emerging experimental techniques. This\napproach may also enable one to circumvent current limits due to radiation\ndamage and solution purification.", "category": "physics_bio-ph" }, { "text": "Jamming and arrest of cell motion in biological tissues: Collective cell motility is crucial to many biological processes including\nmorphogenesis, wound healing, and cancer invasion. Recently, the biology and\nbiophysics communities have begun to use the term cell jamming to describe the\ncollective arrest of cell motion in tissues. Although this term is widely used,\nthe underlying mechanisms are varied. In this review, we highlight three\nindependent mechanisms that can potentially drive arrest of cell motion --\ncrowding, tension-driven rigidity, and reduction of fluctuations -- and propose\na speculative phase diagram that includes all three. Since multiple mechanisms\nmay be operating simultaneously, this emphasizes that experiments should strive\nto identify which mechanism dominates in a given situation. We also discuss how\nspecific cell-scale and molecular-scale biological processes, such as cell-cell\nand cell-substrate interactions, control aspects of these underlying physical\nmechanisms.", "category": "physics_bio-ph" }, { "text": "Monitoring the rotary motors of single FoF1-ATP synthase by synchronized\n multi channel TCSPC: Confocal time resolved single-molecule spectroscopy using pulsed laser\nexcitation and synchronized multi channel time correlated single photon\ncounting (TCSPC) provides detailed information about the conformational changes\nof a biological motor in real time. We studied the formation of adenosine\ntriphosphate, ATP, from ADP and phosphate by FoF1-ATP synthase. The reaction is\nperformed by a stepwise internal rotation of subunits of the lipid\nmembrane-embedded enzyme. Using fluorescence resonance energy transfer, FRET,\nwe detected rotation of this biological motor by sequential changes of\nintramolecular distances within a single FoF1-ATP synthase. Prolonged\nobservation times of single enzymes were achieved by functional immobilization\nto the glass surface. The stepwise rotary subunit movements were identified by\nHidden Markov Models (HMM) which were trained with single-molecule FRET\ntrajectories. To improve the accuracy of the HMM analysis we included the\nsingle-molecule fluorescence lifetime of the FRET donor and used alternating\nlaser excitation to co-localize the FRET acceptor independently within a photon\nburst. The HMM analysis yielded the orientations and dwell times of rotary\nsubunits during stepwise rotation. In addition, the action mode of bactericidal\ndrugs, i.e. inhibitors of FoF1-ATP synthase like aurovertin, could be\ninvestigated by the time resolved single-molecule FRET approach.", "category": "physics_bio-ph" }, { "text": "Error Propagation in the Hypercycle: We study analytically the steady-state regime of a network of n error-prone\nself-replicating templates forming an asymmetric hypercycle and its error tail.\nWe show that the existence of a master template with a higher non-catalyzed\nself-replicative productivity, a, than the error tail ensures the stability of\nchains in which m0$, and\nthat asymmetries in the initial condition therefore can cause rotational\nmovement. These results suggest that anticipation could play an important role\nin collective behaviour, since it induces pattern formation and stabilises the\ndynamics of the system.", "category": "physics_bio-ph" }, { "text": "Learning the shape of protein micro-environments with a holographic\n convolutional neural network: Proteins play a central role in biology from immune recognition to brain\nactivity. While major advances in machine learning have improved our ability to\npredict protein structure from sequence, determining protein function from\nstructure remains a major challenge. Here, we introduce Holographic\nConvolutional Neural Network (H-CNN) for proteins, which is a physically\nmotivated machine learning approach to model amino acid preferences in protein\nstructures. H-CNN reflects physical interactions in a protein structure and\nrecapitulates the functional information stored in evolutionary data. H-CNN\naccurately predicts the impact of mutations on protein function, including\nstability and binding of protein complexes. Our interpretable computational\nmodel for protein structure-function maps could guide design of novel proteins\nwith desired function.", "category": "physics_bio-ph" }, { "text": "Direct observation of silver nanoparticle-ubiquitin corona formation: Upon entering physiological environments, nanoparticles readily assume the\nform of a nanoparticle-protein corona that dictates their biological identity.\nUnderstanding the structure and dynamics of nanoparticle-protein corona is\nessential for predicting the fate, transport, and toxicity of nanomaterials in\nliving systems and for enabling the vast applications of nanomedicine. We\ncombined multiscale molecular dynamics simulations and complementary\nexperiments to characterize the silver nanoparticle-ubiquitin corona formation.\nSpecifically, ubiquitins competed with citrates for the nanoparticle surface\nand bound to the particle in a specific manner. Under a high\nprotein/nanoparticle stoichiometry, ubiquitions formed a multi-layer corona on\nthe particle surface. The binding exhibited an unusual stretched-exponential\nbehavior, suggesting a rich kinetics originated from protein-protein,\nprotein-citrate, and protein-nanoparticle interactions. Furthermore, the\nbinding destabilized the {\\alpha}-helices while increasing the {\\beta}-sheets\nof the proteins. Our results revealed the structural and dynamic complexities\nof nanoparticle-protein corona formation and shed light on the origin of\nnanotoxicity.", "category": "physics_bio-ph" }, { "text": "Force-velocity relations for multiple-molecular-motor transport: A transition rate model of cargo transport by $N$ molecular motors is\nproposed. Under the assumption of steady state, the force-velocity curve of\nmulti-motor system can be derived from the force-velocity curve of single\nmotor. Our work shows, in the case of low load, the velocity of multi-motor\nsystem can decrease or increase with increasing motor number, which is\ndependent on the single motor force-velocity curve. And most commonly, the\nvelocity decreases. This gives a possible explanation to some recent", "category": "physics_bio-ph" }, { "text": "Molecular Simulations of the Ribosome and Associated Translation Factors: The ribosome is a macromolecular complex which is responsible for protein\nsynthesis in all living cells according to their transcribed genetic\ninformation. Using X-ray crystallography and, more recently, cryo-electron\nmicroscopy (cryo-EM), the structure of the ribosome was resolved at atomic\nresolution in many functional and conformational states. Molecular dynamics\nsimulations have added information on dynamics and energetics to the available\nstructural information, thereby have bridged the gap to the kinetics obtained\nfrom single-molecule and bulk experiments. Here, we review recent computational\nstudies that brought notable insights into ribosomal structure and function.", "category": "physics_bio-ph" }, { "text": "Force-induced dynamical properties of multiple cytoskeletal filaments\n are distinct from that of single filaments: How cytoskeletal filaments collectively undergo growth and shrinkage is an\nintriguing question. Collective properties of multiple bio-filaments (actin or\nmicrotubules) undergoing hydrolysis, have not been studied extensively earlier,\nwithin simple theoretical frameworks. In this paper, we show that collective\nproperties of multiple filaments under force are very distinct from the\nproperties of a single filament under similar conditions -- these distinctions\nmanifest as follows: (i) the collapse time during collective catastrophe for a\nmultifilament system is much larger than that of a single filament with the\nsame average length, (ii) force-dependence of the cap-size distribution of\nmultiple filaments are quantitatively different from that of single filament,\n(iii) the diffusion constant associated with the system length fluctuations is\ndistinct for multiple filaments, (iv) switching dynamics of multiple filaments\nbetween capped and uncapped states and the fluctuations therein are also\ndistinct. We build a unified picture by establishing interconnections among all\nthese collective phenomena. Additionally, we show that the collapse times\nduring catastrophes can be sharp indicators of collective stall forces\nexceeding the additive contributions of single filaments.", "category": "physics_bio-ph" }, { "text": "Functional quantum biology in photosynthesis and magnetoreception: Is there a functional role for quantum mechanics or coherent quantum effects\nin biological processes? While this question is as old as quantum theory, only\nrecently have measurements on biological systems on ultra-fast time-scales shed\nlight on a possible answer. In this review we give an overview of the two main\ncandidates for biological systems which may harness such functional quantum\neffects: photosynthesis and magnetoreception. We discuss some of the latest\nevidence both for and against room temperature quantum coherence, and consider\nwhether there is truly a functional role for coherence in these biological\nmechanisms. Finally, we give a brief overview of some more speculative examples\nof functional quantum biology including the sense of smell, long-range quantum\ntunneling in proteins, biological photoreceptors, and the flow of ions across a\ncell membrane.", "category": "physics_bio-ph" }, { "text": "Liquid-solid interaction at nanoscale and its application in vegetal\n biology: The water ascent in tall trees is subject to controversy: the vegetal\nbiologists debate on the validity of the cohesion-tension theory which\nconsiders strong negative pressures in microtubes of xylem carrying the crude\nsap. This article aims to point out that liquids are submitted at the walls to\nintermolecular forces inferring density gradients making heterogeneous liquid\nlayers and therefore disqualifying the Navier-Stokes equations for nanofilms.\nThe crude sap motion takes the disjoining pressure gradient into account and\nthe sap flow dramatically increases such that the watering of nanolayers may be\nanalogous to a microscopic flow. Application to microtubes of xylem avoids the\nproblem of cavitation and enables us to understand why the ascent of sap is\npossible for very high trees.", "category": "physics_bio-ph" }, { "text": "Cytoskeletal network morphology regulates intracellular transport\n dynamics: Intracellular transport is essential for maintaining proper cellular function\nin most eukaryotic cells, with perturbations in active transport resulting in\nseveral types of disease. Efficient delivery of critical cargos to specific\nlocations is accomplished through a combination of passive diffusion and active\ntransport by molecular motors that ballistically move along a network of\ncytoskeletal filaments. Although motor-based transport is known to be necessary\nto overcome cytoplasmic crowding and the limited range of diffusion within\nreasonable time scales, the topological features of the cytoskeletal network\nthat regulate transport efficiency and robustness have not been established.\nUsing a continuum diffusion model, we observed that the time required for\ncellular transport was minimized when the network was localized near the\nnucleus. In simulations that explicitly incorporated network spatial\narchitectures, total filament mass was the primary driver of network transit\ntimes. However, filament traps that redirect cargo back to the nucleus caused\nlarge variations in network transport. Filament polarity was more important\nthan filament orientation in reducing average transit times, and transport\nproperties were optimized in networks with intermediate motor on and off rates.\nOur results provide important insights into the functional constraints on\nintracellular transport under which cells have evolved cytoskeletal structures,\nand have potential applications for enhancing reactions in biomimetic systems\nthrough rational transport network design.", "category": "physics_bio-ph" }, { "text": "A new diamond biosensor with integrated graphitic microchannels for\n detecting quantal exocytic events from chromaffin cells: The quantal release of catecholamines from neuroendocrine cells is a key\nmechanism which has been investigated with a broad range of materials and\ndevices, among which carbon-based materials such as carbon fibers, diamond-like\ncarbon, carbon nanotubes and nanocrystalline diamond. In the present work we\ndemonstrate that a MeV-ion-microbeam lithographic technique can be successfully\nemployed for the fabrication of an all-carbon miniaturized cellular bio-sensor\nbased on graphitic micro-channels embedded in a single-crystal diamond matrix.\nThe device was functionally characterized for the in vitro recording of quantal\nexocytic events from single chromaffin cells, with high sensitivity and\nsignal-to-noise ratio, opening promising perspectives for the realization of\nmonolithic all-carbon cellular biosensors.", "category": "physics_bio-ph" }, { "text": "Basin entropy behavior in a cyclic model of the rock-paper-scissors type: We deal with stochastic network simulations in a model with three distinct\nspecies that compete under cyclic rules which are similar to the rules of the\npopular rock-paper-scissors game. We investigate the Hamming distance density\nand then the basin entropy behavior, running the simulations for some typical\nvalues of the parameters mobility, predation and reproduction and for very long\ntime evolutions. The results show that the basin entropy is another interesting\ntool of current interest to investigate chaotic features of the network\nsimulations that are usually considered to describe aspects of biodiversity in\nthe cyclic three-species model.", "category": "physics_bio-ph" }, { "text": "Molecular Communication Using Brownian Motion with Drift: Inspired by biological communication systems, molecular communication has\nbeen proposed as a viable scheme to communicate between nano-sized devices\nseparated by a very short distance. Here, molecules are released by the\ntransmitter into the medium, which are then sensed by the receiver. This paper\ndevelops a preliminary version of such a communication system focusing on the\nrelease of either one or two molecules into a fluid medium with drift. We\nanalyze the mutual information between transmitter and the receiver when\ninformation is encoded in the time of release of the molecule. Simplifying\nassumptions are required in order to calculate the mutual information, and\ntheoretical results are provided to show that these calculations are upper\nbounds on the true mutual information. Furthermore, optimized degree\ndistributions are provided, which suggest transmission strategies for a variety\nof drift velocities.", "category": "physics_bio-ph" }, { "text": "Theory of cyborg: a new approach to fish locomotion control: Cyborg in the brain-machine interface field has attracted more attention in\nrecent years. To control a creature via a machine called cyborg method, three\nstages are considerable: stimulation of neurons, neural response, and the\nbehavioral reaction of the subject. Our main concern was to know how electrical\nstimulation induces neural activity and leads to a behavioral response.\nAdditionally, we were interested to explore which type of electrical\nstimulation is optimal from different aspects such as maximum response with\nminimum induction stimulus field, minimum damage of the tissue and the\nelectrode, reduction of the noxiousness of stimuli or pain in the living\ncreature. In this article, we proposed a new model for the induction of neural\nactivity led to locomotion responses through electrical stimulation.\nFurthermore, based on this model, we developed a new approach of electrical\nneural stimulation to provide a better locomotion control of living beings.\nThis approach was verified through the empirical data of fish cyborg. We\nstimulated the fish brain by use of an ultra-high frequency signal which\ncareered by a random low frequency. According to our model, we could control\nthe locomotion of fish in a novel and innovative way. In this study, we\ncategorized the different cyborg methods based on the nervous system areas and\nthe stimulation signal properties to reach the better and optimal behavioral\ncontrol of creature. According to this, we proposed a new stimulation method\ntheoretically and confirmed it experimentally.", "category": "physics_bio-ph" }, { "text": "Collective Motion: With the aim of understanding the emergence of collective motion from local\ninteractions of organisms in a \"noisy\" environment, we study biologically\ninspired, inherently non-equilibrium models consisting of self-propelled\nparticles. In these models particles interact with their neighbors by turning\ntowards the local average direction of motion. In the limit of vanishing\nvelocities this behavior results in a dynamics analogous to some Monte Carlo\nrealization of equilibrium ferromagnets. However, numerical simulations\nindicate the existence of new types of phase transitions which are not present\nin the corresponding ferromagnets. In particular, here we demonstrate both\nnumerically and analytically that even in certain one dimensional\nself-propelled particle systems an ordered phase exists for finite noise\nlevels.", "category": "physics_bio-ph" }, { "text": "Novel physics arising from phase transitions in biology: Phase transitions, such as the freezing of water and the magnetisation of a\nferromagnet upon lowering the ambient temperature, are familiar physical\nphenomena. Interestingly, such a collective change of behaviour at a phase\ntransition is also of importance to living systems. From cytoplasmic\norganisation inside a cell to the collective migration of cell tissue during\norganismal development and wound healing, phase transitions have emerged as key\nmechanisms underlying many crucial biological processes. However, a living\nsystem is fundamentally different from a thermal system, with driven chemical\nreactions (e.g., metabolism) and motility being two hallmarks of its\nnonequilibrium nature. In this review, we will discuss how driven chemical\nreactions can arrest universal coarsening kinetics expected from thermal phase\nseparation, and how motility leads to the emergence of a novel universality\nclass when the rotational symmetry is spontaneously broken in an incompressible\nfluid.", "category": "physics_bio-ph" }, { "text": "Biomimetic Hierarchical Structuring of PLA by Ultra-Short Laser Pulses\n for Processing of Tissue Engineered Matrices: Study of Cellular and\n Antibacterial Behavior: The influence of ultra-short laser modification on the surface morphology and\npossible chemical alteration of poly-lactic acid (PLA) matrix in respect to the\noptimization of cellular and antibacterial behavior were investigated in this\nstudy. Scanning electron microscopy (SEM) morphological examination of the\nprocessed PLA surface showed the formation of diverse hierarchical surface\nmicrostructures, generated by irradiation with a range of laser fluences (F)\nand scanning velocities (V) values. By controlling the laser parameters,\ndiverse surface roughness can be achieved, thus influencing cellular dynamics.\nThis surface feedback can be applied to finely tune and control diverse\nbiomaterial surface properties like wettability, reflectivity, and biomimetics.\nThe triggering of thermal effects, leading to the ejection of material with\nsubsequent solidification and formation of raised rims and 3D-like hollow\nstructures along the processed zones, demonstrated a direct correlation to the\nwettability of the PLA. A transition from superhydrophobic (thetha > 150 deg.)\nto super hydrophilic (thetha < 20 deg.) surfaces can be achieved by the\ncreation of grooves with V = 0.6 mm/s, F = 1.7 J/cm2. The achieved hierarchical\narchitecture affected morphology and thickness of the processed samples which\nwere linked to the nature of ultra-short laser-material interaction effects,\nnamely the precipitation of temperature distribution during material processing\ncan be strongly minimized with ultrashort pulses leading to non-thermal and\nspatially localized effects that can facilitate volume ablation without\ncollateral thermal damage.", "category": "physics_bio-ph" }, { "text": "Multifunctional nanostructures for intracellular delivery and sensing in\n electrogenic cells: In electrophysiology, multielectrode array devices (MEA) are the gold\nstandard for the study of large ensambles of electrogenic cells. In the last\ndecades, thanks to the adoption of nanotechnologies, the study of physiological\nand pathological conditions of electro-active cells in culture have becomes\nincreasingly accurate. In parallel, studies exploited the integration of\nnanostructures with delivering capabilities with single-cell specificity and\nhigh throughput in biosensing platforms. Delivery and recording have\nindependently led to great advances in neurobiology, however, their integration\non a single chip would give complete insights into pathologies development and\nfundamental advancements in drug screening methods. In this work, we\ndemonstrate how a microfluidic-MEA technology may be used to record both\nspontaneous and chemically induced activity in vitro. We propose a device that\ncan deliver molecules to only a few chosen cells and detecting the response in\ncellular activity at multiple sites simultaneously. In addition, will be\ndiscussed how the adoption of nanoporous metamaterial in place of\nnanostructures might lower costs and speed up production. Furthermore, this\nsame material, will be identified for the first time in this work as\nphotoelectrical modulating material for eliciting electrogenic cells firing\nactivity. Specifically, by converting NIR laser pulses into stimulatory\ncurrents, plasmonic metamaterials may be employed to induce action potentials.\nThis method enables remote access to optical pacing with precise spatiotemporal\ncontrol, allowing to be used as a valid alternative of the traditional\ngenetic-based optical stimulation techniques. Therefore, in addition to\npharmaceutical applications, these final characteristics may pave the way for a\nnew generation of minimally invasive, cellular type-independent all-optical\nplasmonic pacemakers and muscle actuators.", "category": "physics_bio-ph" }, { "text": "Model of the best-of-N nest-site selection process in honeybees: The ability of a honeybee swarm to select the best nest site plays a\nfundamental role in determining the future colony's fitness. To date, the\nnest-site selection process has mostly been modelled and theoretically analysed\nfor the case of binary decisions. However, when the number of alternative nests\nis larger than two, the decision process dynamics qualitatively change. In this\nwork, we extend previous analyses of a value-sensitive decision-making\nmechanism to a decision process among N nests. First, we present the\ndecision-making dynamics in the symmetric case of N equal-quality nests. Then,\nwe generalise our findings to a best-of-N decision scenario with one superior\nnest and N-1 inferior nests, previously studied empirically in bees and ants.\nWhereas previous binary models highlighted the crucial role of inhibitory\nstop-signalling, the key parameter in our new analysis is the relative time\ninvested by swarm members in individual discovery and in signalling behaviours.\nOur new analysis reveals conflicting pressures on this ratio in symmetric and\nbest-of-N decisions, which could be solved through a time-dependent signalling\nstrategy. Additionally, our analysis suggests how ecological factors\ndetermining the density of suitable nest sites may have led to selective\npressures for an optimal stable signalling ratio.", "category": "physics_bio-ph" }, { "text": "Lab-in-a-Tube: A portable imaging spectrophotometer for cost-effective,\n high-throughput, and label-free analysis of centrifugation processes: Centrifuges serve as essential instruments in modern experimental sciences,\nfacilitating a wide range of routine sample processing tasks that necessitate\nmaterial sedimentation. However, the study for real time observation of the\ndynamical process during centrifugation has remained elusive. In this study, we\ndeveloped an innovative Lab_in_a_Tube imaging spectrophotometer that\nincorporates capabilities of real time image analysis and programmable\ninterruption. This portable LIAT device costs less than 30 US dollars. Based on\nour knowledge, it is the first Wi Fi camera built_in in common lab centrifuges\nwith active closed_loop control. We tested our LIAT imaging spectrophotometer\nwith solute solvent interaction investigation obtained from lab centrifuges\nwith quantitative data plotting in a real time manner. Single re circulating\nflow was real time observed, forming the ring shaped pattern during\ncentrifugation. To the best of our knowledge, this is the very first\nobservation of similar phenomena. We developed theoretical simulations for the\nsingle particle in a rotating reference frame, which correlated well with\nexperimental results. We also demonstrated the first demonstration to visualize\nthe blood sedimentation process in clinical lab centrifuges. This remarkable\ncost effectiveness opens up exciting opportunities for centrifugation\nmicrobiology research and paves the way for the creation of a network of\ncomputational imaging spectrometers at an affordable price for large scale and\ncontinuous monitoring of centrifugal processes in general.", "category": "physics_bio-ph" }, { "text": "BCL::MP-Fold: membrane protein structure prediction guided by EPR\n restraints: For many membrane proteins the determination of their topology remains a\nchallenge for methods like X-ray crystallography and nuclear magnetic resonance\n(NMR) spectroscopy. Electron paramagnetic resonance (EPR) spectroscopy has\nevolved as an alternative technique to study structure and dynamics of membrane\nproteins. The present study demonstrates the feasibility of membrane protein\ntopology determination using limited EPR distance and accessibility\nmeasurements. The BCL::MP-Fold (BioChemical Library membrane protein fold)\nalgorithm assembles secondary structure elements (SSEs) in the membrane using a\nMonte Carlo Metropolis (MCM) approach. Sampled models are evaluated using\nknowledge-based potential functions and agreement with the EPR data and a\nknowledge-based energy function. Twenty-nine membrane proteins of up to 696\nresidues are used to test the algorithm. The RMSD100 value of the most accurate\nmodel is better than 8 {\\AA} for twenty-seven, better than 6 {\\AA} for\ntwenty-two and better than 4 {\\AA} for fifteen out of twenty-nine proteins,\ndemonstrating the algorithms ability to sample the native topology. The average\nenrichment could be improved from 1.3 to 2.5, showing the improved\ndiscrimination power by using EPR data.", "category": "physics_bio-ph" }, { "text": "Hydrodynamic flow and concentration gradients in the gut enhance neutral\n bacterial diversity: The gut microbiota features important genetic diversity, and the specific\nspatial features of the gut may shape evolution within this environment. We\ninvestigate the fixation probability of neutral bacterial mutants within a\nminimal model of the gut that includes hydrodynamic flow and resulting\ngradients of food and bacterial concentrations. We find that this fixation\nprobability is substantially increased compared to an equivalent well-mixed\nsystem, in the regime where the profiles of food and bacterial concentration\nare strongly spatially-dependent. Fixation probability then becomes independent\nof total population size. We show that our results can be rationalized by\nintroducing an active population, which consists of those bacteria that are\nactively consuming food and dividing. The active population size yields an\neffective population size for neutral mutant fixation probability in the gut.", "category": "physics_bio-ph" }, { "text": "Statistical properties of metastable intermediates in DNA unzipping: We unzip DNA molecules using optical tweezers and determine the sizes of the\ncooperatively unzipping and zipping regions separating consecutive metastable\nintermediates along the unzipping pathway. Sizes are found to be distributed\nfollowing a power law, ranging from one base pair up to more than a hundred\nbase pairs. We find that a large fraction of unzipping regions smaller than 10\nbp are seldom detected because of the high compliance of the released single\nstranded DNA. We show how the compliance of a single nucleotide sets a limit\nvalue around 0.1 N/m for the stiffness of any local force probe aiming to\ndiscriminate one base pair at a time in DNA unzipping experiments.", "category": "physics_bio-ph" }, { "text": "Atomic Torsional Modal Analysis for high-resolution proteins: We introduce a formulation for normal mode analyses of globular proteins that\nsignificantly improves on an earlier, 1-parameter formulation (M. Tirion, PRL\n77, 1905 (1996)) that characterized the slow modes associated with protein data\nbank structures. Here we develop that empirical potential function which is\nminimized at the outset to include two features essential to reproduce the\neigenspectra and associated density of states over all frequencies, not merely\nthe slow ones. First, introduction of preferred dihedral-angle configurations\nvia use of torsional stiffness constants eliminates anomalous dispersion\ncharacteristics due to insufficiently bound surface sidechains. Second, we take\ninto account the atomic identities and the distance of separation of all\npairwise interactions. With these modifications we obtain stable, reliable\neigenmodes over a wide range of frequencies.", "category": "physics_bio-ph" }, { "text": "Undulation Instability of Epithelial Tissues: Treating the epithelium as an incompressible fluid adjacent to a viscoelastic\nstroma, we find a novel hydrodynamic instability that leads to the formation of\nprotrusions of the epithelium into the stroma. This instability is a candidate\nfor epithelial fingering observed in vivo. It occurs for sufficiently large\nviscosity, cell-division rate and thickness of the dividing region in the\nepithelium. Our work provides physical insight into a potential mechanism by\nwhich interfaces between epithelia and stromas undulate, and potentially by\nwhich tissue dysplasia leads to cancerous invasion.", "category": "physics_bio-ph" }, { "text": "Binding of Pheophorbide-a methyl ester to nucleic acids of different\n secondary structures: A spectroscopic study: Binding of neutral Pheophorbide-a methyl ester (MePheo-a) to various\nsynthetic polynucleotides, double-stranded poly(A)-poly(U), poly(G)-poly(C) and\nfour-stranded poly(G), as well as to calf thymus DNA, was studied using the\nmethods of absorption and polarized fluorescent spectroscopy. Measurements were\nperformed in aqueous bufferes solutions (pH 6.9) of low ionic strength (2 mM\nNa+) in a wide range of molar phosphate-to-dye ratios (P/D). Absorption and\nfluorescence characteristics of complexes formed between the dye and\nbiopolymers were determined. Binding of MePheo-a to four-stranded poly(G) is\nshown to be accompanied by the most significant spectral transformations:\nhypochromism of dye absorption,large batochromic shift of Soret absorption band\n(~26 nm) and fluorescence band (~9 nm) maxima, 48-fold enhancement of the dye\nemission intensity. In contrast, its binding to the double-stranded\npolynucleotides and native DNA induces only small shifts of absorption and\nfluorescence bands, as well as no more than 4-fold rise of fluorescence\nintensity. Substantial spectral changes and high value of fluorescence\npolarization degree (0.26) observed upon binding of MePheo-a to quadruplex\npoly(G) allow us to suggest the intercalation of the dye chromophore between\nguanine tetrads. At the same time, small spectral changed and insignificant\nincrease of MePheo-a fluorescence polarization degree (0.12) upon binding of\nthe dye to double-stranded biopolymers point to another binding type.\nIncorporation of MePheo-a to a helix groove is supposed to occur, presumably in\nthe dimeric form. Substantial enhancement of MePheo-a emission upon binding to\nfour-stranded poly(G) allows us to propose this compouns as a new fluorescent\nprobe G-quadruplex structures.", "category": "physics_bio-ph" }, { "text": "E. coli chemotaxis is information-limited: Organisms must acquire and use environmental information to guide their\nbehaviors. However, it is unclear whether and how information quantitatively\nlimits behavioral performance. Here, we relate information to behavioral\nperformance in Escherichia coli chemotaxis. First, we derive a theoretical\nlimit for the maximum achievable gradient-climbing speed given a cell's\ninformation acquisition rate. Next, we measure cells' gradient-climbing speeds\nand the rate of information acquisition by the chemotaxis pathway. We find that\nE. coli make behavioral decisions with much less than the 1 bit required to\ndetermine whether they are swimming up-gradient. However, they use this\ninformation efficiently, performing near the theoretical limit. Thus,\ninformation can limit organisms' performance, and sensory-motor pathways may\nhave evolved to efficiently use information from the environment.", "category": "physics_bio-ph" }, { "text": "Biophysical characterization of DNA origami nanostructures reveals\n inaccessibility to intercalation binding sites: Intercalation of drug molecules into synthetic DNA nanostructures formed\nthrough self-assembled origami has been postulated as a valuable future method\nfor targeted drug delivery. This is due to the excellent biocompatibility of\nsynthetic DNA nanostructures, and high potential for flexible programmability\nincluding facile drug release into or near to target cells. Such favourable\nproperties may enable high initial loading and efficient release for a\npredictable number of drug molecules per nanostructure carrier, important for\nefficient delivery of safe and effective drug doses to minimise non-specific\nrelease away from target cells. However, basic questions remain as to how\nintercalation-mediated loading depends on the DNA carrier structure. Here we\nuse the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D\nDNA origami tile as a simple model system to investigate intercalation-mediated\nloading. We employed multiple biophysical techniques including single-molecule\nfluorescence microscopy, atomic force microscopy, gel electrophoresis and\ncontrollable damage using low temperature plasma on synthetic DNA origami\nsamples. Our results indicate that not all potential DNA binding sites are\naccessible for dye intercalation, which has implications for future DNA\nnanostructures designed for targeted drug delivery.", "category": "physics_bio-ph" }, { "text": "High-Mg Calcite Nanoparticles Within a Low-Mg Calcite Matrix via\n Spinodal Decomposition: A Widespread Phenomenon in Biomineralization: During the process of biomineralization, organisms utilize various\nbiostrategies to enhance the mechanical durability of their skeletons. In this\nwork, we establish that the presence of high-Mg nanoparticles embedded within\nlower Mg calcite matrices is a widespread strategy utilized by various\norganisms from different kingdoms and phyla to improve the mechanical\nproperties of their high Mg calcite skeletons. We show that such phase\nseparation and the formation of high-Mg nanoparticles are achieved through\nspinodal decomposition of an amorphous Mg calcite precursor. Such decomposition\nis independent of the biological characteristics of the studied organisms\nbelonging to different phyla and even kingdoms, but rather originates from\ntheir similar chemical composition and a specific Mg content within their\nskeletons, which generally ranges from 14 to 48 mol percent of Mg. We show\nevidence of high Mg calcite nanoparticles in the cases of 6 biologically\ndifferent organisms all demonstrating more than 14 mol percent Mg calcite, and\nconsider it likely that this phenomenon is immeasurably more prevalent in\nnature. We also establish the absence of these high Mg nanoparticles in\norganisms whose Mg content is lower than 14 mol percent, providing further\nevidence that whether or not spinodal decomposition of an amorphous Mg calcite\nprecursor takes place is determined by the amount of Mg it contains. The\nvaluable knowledge gained from this biostrategy significantly impacts the\nunderstanding of how biominerals, though comprised of intrinsically brittle\nmaterials, can effectively resist fracture.", "category": "physics_bio-ph" }, { "text": "Broken Detailed Balance of Filament Dynamics in Active Networks: Myosin motor proteins drive vigorous steady-state fluctuations in the actin\ncytoskeleton of cells. Endogenous embedded semiflexible filaments such as\nmicrotubules, or added filaments such as single-walled carbon nanotubes are\nused as novel tools to non-invasively track equilibrium and non-equilibrium\nfluctuations in such biopolymer networks. Here we analytically calculate shape\nfluctuations of semiflexible probe filaments in a viscoelastic environment,\ndriven out of equilibrium by motor activity. Transverse bending fluctuations of\nthe probe filaments can be decomposed into dynamic normal modes. We find that\nthese modes no longer evolve independently under non-equilibrium driving. This\neffective mode coupling results in non-zero circulatory currents in a\nconformational phase space, reflecting a violation of detailed balance. We\npresent predictions for the characteristic frequencies associated with these\ncurrents and investigate how the temporal signatures of motor activity\ndetermine mode correlations, which we find to be consistent with recent\nexperiments on microtubules embedded in cytoskeletal networks.", "category": "physics_bio-ph" }, { "text": "Noisy NFkB oscillations stabilize and sensitize cytokine signaling in\n space: NF-kB is a major transcription factor mediating inflammatory response. In\nresponse to pro-inflammatory stimulus, it exhibits characteristic response -- a\npulse followed by noisy oscillations in concentrations of considerably smaller\namplitude. NF-kB is an important mediator of cellular communication, as it is\nboth activated by and upregulates production of cytokines, signals used by\nwhite blood cells to find the source of inflammation. While the oscillatory\ndynamics of NF-$\\kappa$B has been extensively investigated both experimentally\nand theoretically, the role of the noise and the lower secondary amplitude has\nnot been addressed.\n We use a cellular automaton model to address these issues in the context of\nspatially distributed communicating cells. We find that noisy secondary\noscillations stabilize concentric wave patterns, thus improving signal quality.\nFurthermore, both lower secondary amplitude as well as noise in the oscillation\nperiod might be working against chronic inflammation, the state of\nself-sustained and stimulus-independent excitations.\n Our findings suggest that the characteristic irregular secondary oscillations\nof lower amplitude are not accidental. On the contrary, they might have evolved\nto increase robustness of the inflammatory response and the system's ability to\nreturn to pre-stimulated state.", "category": "physics_bio-ph" }, { "text": "Fractional Cable Model for Signal Conduction in Spiny Neuronal Dendrites: The cable model is widely used in several fields of science to describe the\npropagation of signals. A relevant medical and biological example is the\nanomalous subdiffusion in spiny neuronal dendrites observed in several studies\nof the last decade. Anomalous subdiffusion can be modelled in several ways\nintroducing some fractional component into the classical cable model. The\nChauchy problem associated to these kind of models has been investigated by\nmany authors, but up to our knowledge an explicit solution for the signalling\nproblem has not yet been published. Here we propose how this solution can be\nderived applying the generalized convolution theorem (known as Efros theorem)\nfor Laplace transforms. The fractional cable model considered in this paper is\ndefined by replacing the first order time derivative with a fractional\nderivative of order $\\alpha\\in(0,1)$ of Caputo type. The signalling problem is\nsolved for any input function applied to the accessible end of a semi-infinite\ncable, which satisfies the requirements of the Efros theorem. The solutions\ncorresponding to the simple cases of impulsive and step inputs are explicitly\ncalculated in integral form containing Wright functions. Thanks to the\nvariability of the parameter $\\alpha$, the corresponding solutions are expected\nto adapt to the qualitative behaviour of the membrane potential observed in\nexperiments better than in the standard case $\\alpha=1$.", "category": "physics_bio-ph" }, { "text": "Modeling generic aspects of ideal fibril formation: Many different proteins self-aggregate into insoluble fibrils growing\napically by reversible addition of elementary building blocks. But beyond this\ncommon principle, the modalities of fibril formation are very disparate, with\nvarious intermediate forms which can be reshuffled by minor modifications of\nphysico-chemical conditions or amino-acid sequences. To bypass this complexity,\nthe multifaceted phenomenon of fibril formation is reduced here to its most\nelementary principles defined for a linear prototype of fibril. Selected\ngeneric features, including nucleation, elongation and conformational\nrecruitment, are modeled using minimalist hypotheses and tools, by separating\nequilibrium from kinetic aspects and in vitro from in vivo conditions. These\nreductionist approaches allow to bring out known and new rudiments, including\nthe kinetic and equilibrium effects of nucleation, the dual influence of\nelongation on nucleation, the kinetic limitations on nucleation and fibril\nnumbers and the accumulation of complexes in vivo by rescue from degradation.\nOverlooked aspects of these processes are also pointed: the exponential\ndistribution of fibril lengths can be recovered using various models because it\nis attributable to randomness only. It is also suggested that the same term\n\"critical concentration\" is used for different things, involved in either\nnucleation or elongation.", "category": "physics_bio-ph" }, { "text": "Acoustic Features and Perceptive Cues of Songs and Dialogues in Whistled\n Speech: Convergences with Sung Speech: Whistled speech is a little studied local use of language shaped by several\ncultures of the world either for distant dialogues or for rendering traditional\nsongs. This practice consists of an emulation of the voice thanks to a simple\nmodulated pitch. It is therefore the result of a transformation of the vocal\nsignal that implies simplifications in the frequency domain. The whistlers\nadapt their productions to the way each language combines the qualities of\nheight perceived simultaneously by the human ear in the complex frequency\nspectrum of the spoken or sung voice (pitch, timbre). As a consequence, this\npractice underlines key acoustic cues for the intelligibility of the concerned\nlanguages. The present study provides an analysis of the acoustic and phonetic\nfeatures selected by whistled speech in several traditions either in purely\noral whistles (Spanish, Turkish, Mazatec) or in whistles produced with an\ninstrument like a leaf (Akha, Hmong). It underlines the convergences with the\nstrategies of the singing voice to reach the audience or to render the phonetic\ninformation carried by the vowel (tone, identity) and some aesthetic effects\nlike ornamentation.", "category": "physics_bio-ph" }, { "text": "Research Notes: Gradient sensing in Bayesian chemotaxis: Bayesian chemotaxis is an information-based target search problem inspired by\nbiological chemotaxis. It is defined by a decision strategy coupled to the\ndynamic estimation of target position from detections of signaling molecules.\nWe extend the case of a point-like agent previously introduced in [Vergassola\net al., Nature 2007], which establishes concentration sensing as the dominant\ncontribution to information processing, to the case of a circular agent of\nsmall finite size. We identify gradient sensing and a Laplacian correction to\nconcentration sensing as the two leading-order expansion terms in the expected\nentropy variation. Numerically, we find that the impact of gradient sensing is\nmost relevant because it provides direct directional information to break\nsymmetry in likelihood distributions, which are generally circle-shaped by\nconcentration sensing.", "category": "physics_bio-ph" }, { "text": "Biological signaling by interfacial sound pulses. A physics approach: Biological signaling is imagined as a combination of activation and\ntransport. The former is triggered by local molecular interactions and the\nlatter is the result of molecular diffusion. However, other fundamental\nphysical principles of communication have yet to be addressed. We have recently\nshown, that lipid interfaces allow for the excitation and propagation of sound\npulses. Here we demonstrate, that these reversible perturbations can control\nthe activity of membrane embedded enzymes without the necessity of molecular\ntransport. They therefore allow for the rapid communication between distant\nbiological entities (e.g. receptor and enzyme) at the speed of sound, which is\nhere in the order of 1 m/s within the membrane. The mechanism reported provides\na new physical framework for biological signaling.", "category": "physics_bio-ph" }, { "text": "Retardation of Bulk Water Dynamics by Disaccharide Osmolytes: The bioprotective nature of disaccharides is hypothesized to derive from the\nmodification of the hydrogen bonding network of water which protects\nbiomolecules through lowered water activity at the protein interface. Using\nultrafast fluorescence spectroscopy we measured the relaxation of bulk water\ndynamics around the induced dipole moment of two fluorescent probes (Lucifer\nYellow Ethylenediamine and Tryptophan). Our results indicate a reduction in\nbulk water reorganization rate of approximately of 30%. We observe this\nretardation in the low concentration regime measured at 0.1M and 0.25 M, far\nbelow the onset of glassy dynamics. This reduction in water activity could be\nsignificant in crowded biological systems, contributing to global change in\nprotein energy landscape, resulting in a significant enhancement of protein\nstability under environmental stress. We observed similar dynamic reduction for\ntwo disaccharide osmolytes, sucrose and trehalose, with trehalose being the\nmore effective dynamic reducer.", "category": "physics_bio-ph" }, { "text": "Bayesian gradient sensing in the presence of rotational diffusion: Biological cells estimate concentration gradients of signaling molecules with\na precision that is limited not only by sensing noise, but additionally by the\ncell's own stochastic motion. We ask for the theoretical limits of gradient\nestimation in the presence of both motility and sensing noise. We introduce a\nminimal model of a stationary chemotactic agent in the plane subject to\nrotational diffusion, which uses Bayesian estimation to optimally infer a\ngradient direction from noisy concentration measurements. Contrary to the known\ncase of gradient sensing by temporal comparison, we show that for spatial\ncomparison, the ultimate precision of gradient sensing scales not with the\nrotational diffusion time, but with its square-root. To achieve this precision,\nan individual agent needs to know its own rotational diffusion coefficient.\nThis agent can accurately estimate the expected variability within an ensemble\nof agents. If an agent, however, does not account for its own motility noise,\nBayesian estimation fails in a characteristic manner.", "category": "physics_bio-ph" }, { "text": "Short-term memory effects in the phototactic behavior of microalgae: Phototaxis, the directed motion in response to a light stimulus, is crucial\nfor motile microorganisms that rely on photosynthesis, such as the unicellular\nmicroalga Chlamydomonas reinhardtii. It is well known that microalgae adapt to\nambient light stimuli. On time scales of several dozen minutes, when stimulated\nlong enough, the response of the microalga evolves as if the light intensity\nwere decreasing (Mayer, Nature 1968). Here, we show experimentally that\nmicroalgae also have a short-term memory, on the time scale of a couple of\nminutes, which is the opposite of adaptation. At these short time scales, when\nstimulated consecutively, the response of C. reinhardtii evolves as if the\nlight intensity were increasing. Our experimental results are rationalized by\nthe introduction of a simplified model of phototaxis. Memory comes from the\ninterplay between an internal biochemical time scale and the time scale of the\nstimulus; as such, these memory effects are likely to be widespread in\nphototactic microorganisms.", "category": "physics_bio-ph" }, { "text": "Influence of Correlated Noises on Growth of a Tumor: We studied the effect of additive and multiplicative noises on the growth of\na tumor based on a logistic growth model. The steady-state probability\ndistribution and the average population of the tumor cells were given to\nexplain the important roles of correlated noises in the tumor growth. We found\nthat multiplicative noise induces a phase transition of the tumor growth from\nan uni-stable state to a bi-stable state; the relationship between the\nintensity of multiplicative noise and the population of the tumor cells showed\na stochastic resonance-like characteristic. It was also confirmed that additive\nnoise weakened rather than extinguish the tumor growth. Homologous noises,\nhowever, promote the growth of a tumor. We also discussed about the\nrelationship between the tumor treatment and the model.", "category": "physics_bio-ph" }, { "text": "Interfacing Graphene-Based Materials With Neural Cells: The scientific community has witnessed an exponential increase in the\napplications of graphene and graphene-based materials in a wide range of\nfields. For what concerns neuroscience, the interest raised by these materials\nis two-fold. On one side, nanosheets made of graphene or graphene derivatives\n(graphene oxide, or its reduced form) can be used as carriers for drug\ndelivery. Here, an important aspect is to evaluate their toxicity, which\nstrongly depends on flake composition, chemical functionalization and\ndimensions. On the other side, graphene can be exploited as a substrate for\ntissue engineering. In this case, conductivity is probably the most relevant\namongst the various properties of the different graphene materials, as it may\nallow to instruct and interrogate neural networks, as well as to drive neural\ngrowth and differentiation. In this review, we try to give a comprehensive view\nof the accomplishments and new challenges of the field, as well as which in our\nview are the most exciting directions to take in the immediate future. These\ninclude the need to engineer multifunctional nanoparticles able to cross the\nblood-brain-barrier to reach neural cells, and to achieve on-demand delivery of\nspecific drugs. We describe the state-of-the-art in the use of graphene\nmaterials to engineer three-dimensional scaffolds to drive neuronal growth and\nregeneration in vivo, and the possibility of using graphene as a component of\nhybrid composites/multi-layer organic electronics devices. Last but not least,\nwe address the need of an accurate theoretical modeling of the interface\nbetween graphene and biological material, by modeling the interaction of\ngraphene with proteins and cell membranes at the nanoscale, and describing the\nphysical mechanism(s) of charge transfer by which the various graphene\nmaterials can influence the excitability and physiology of neural cells.", "category": "physics_bio-ph" }, { "text": "Hierarchical structure and biomineralization in cricket tooth: Cricket is a truculent insect with stiff and sharp teeth as a fighting\nweapon. The structure and possible biomineralization of the cricket teeth are\nalways interested. Synchrotron radiation X-ray fluorescence, X-ray diffraction\nand small angle X-ray scattering techniques were used to probe the element\ndistribution, possible crystalline structures and size distribution of\nscatterers in cricket teeth. Scanning electron microscope was used to observe\nthe nanoscaled structure. The results demonstrate that Zn is the main heavy\nelement in cricket teeth. The surface of the cricket teeth has a crystalline\ncompound like ZnFe2(AsO4)2(OH)2(H2O)4. While, the interior of the teeth has a\ncrystalline compound like ZnCl2, which is from the biomineralization. The\nZnCl2-like biomineral forms nanoscaled microfibrils and their axial direction\npoints at the top of tooth cusp. The microfibrils aggregate random into\nintermediate filaments, forming a hierarchical structure. A sketch map of the\ncricket tooth cusp was proposed and a detailed discussion was given in this\npaper.", "category": "physics_bio-ph" }, { "text": "Orientational Mapping Augmented Sub-Wavelength Hyper-Spectral Imaging of\n Silk: Molecular alignment underpins optical, mechanical, and thermal properties of\nmaterials, however, its direct measurement from volumes with micrometer\ndimensions is not accessible, especially, for structurally complex\nbio-materials. How the molecular alignment is linked to extraordinary\nproperties of silk and its amorphous-crystalline composition has to be accessed\nby a direct measurement from a single silk fiber. Here, we show orientation\nmapping of the internal silk fiber structure via polarisation-dependent IR\nabsorbance at high spatial resolution of 4.2 micrometers and 1.9 micrometers in\na hyper-spectral IR imaging by attenuated total reflection using synchrotron\nradiation in the spectral fingerprint region around 6 micrometers wavelength.\nFree-standing longitudinal micro-slices of silk fibers, thinner than the fiber\ncross section, were prepared by microtome for the four polarisation method to\ndirectly measure the orientational sensitivity of absorbance in the molecular\nfingerprint spectral window of the amide bands of b-sheets and amorphous\npolypeptides of silk. Flat lateral micro-slices of silk eliminates shape\nrelated artefact in determination of absorbance anisotropy and order parameters\nof the amide bands.", "category": "physics_bio-ph" }, { "text": "Holographic intravital microscopy for 2-D and 3-D imaging intact\n circulating blood cells in microcapillaries of live mice: Intravital microscopy is an essential tool that reveals behaviours of live\ncells under conditions close to natural physiological states. So far, although\nvarious approaches for imaging cells in vivo have been proposed, most require\nthe use of labelling and also provide only qualitative imaging information.\nHolographic imaging approach based on measuring the refractive index\ndistributions of cells, however, circumvent these problems and offer\nquantitative and label-free imaging capability. Here, we demonstrate in vivo\ntwo- and three-dimensional holographic imaging of circulating blood cells in\nintact microcapillaries of live mice. The measured refractive index\ndistributions of blood cells provide morphological and biochemical properties\nincluding three-dimensional cell shape, haemoglobin concentration, and\nhaemoglobin contents at the individual cell level. With the present method,\nalterations in blood flow dynamics in live healthy and sepsis-model mouse were\nalso investigated.", "category": "physics_bio-ph" }, { "text": "Simple Mechanical Equivalents of Stepping Rotary Dynamics in\n F$_1$-ATPase: Two simple (rotator and one-particle) mechanistic models are suggested to\ndescribe simultaneously at a minimal level of sophistication two basic\nfunctions of F$_1$-ATPase: a motor regime driven by ATP hydrolysis and its\ninverted function as ATP synthesis. This description is consistent with the\nso-called rotary binding-change mechanism, a milestone of functioning ATP\nsynthase, and uses a stepping (driving) function associated with two sequences\nof time instants, at which hydrolysis and synthesis reactions occur. It is\nuseful to analyse experimental data and numerical simulations indeed predict\ncorresponding dynamic behavior.", "category": "physics_bio-ph" }, { "text": "Collective Synchronous Spiking in a Brain Network of Coupled Nonlinear\n Oscillators: A network of propagating nonlinear oscillatory modes (waves) in the human\nbrain is shown to generate collectively synchronized spiking activity\n(hypersynchronous spiking) when both amplitude and phase coupling between modes\nare taken into account. The nonlinear behavior of the modes participating in\nthe network are the result of the nonresonant dynamics of weakly evanescent\ncortical waves that, as shown recently, adhere to an inverse frequency-wave\nnumber dispersion relation when propagating through an inhomogeneous\nanisotropic media characteristic of the brain cortex. This description provides\na missing link between simplistic models of synchronization in networks of\nsmall amplitude phase coupled oscillators and in networks built with various\nempirically fitted models of pulse or amplitude coupled spiking neurons.\nOverall the phase-amplitude coupling mechanism presented in the Letter shows\nsignificantly more efficient synchronization compared to current standard\napproaches and demonstrates an emergence of collective synchronized spiking\nfrom subthreshold oscillations that neither phase nor amplitude coupling alone\nare capable of explaining.", "category": "physics_bio-ph" }, { "text": "Quantifying fluctuations in reversible enzymatic cycles and clocks: Biochemical reactions are fundamentally noisy at a molecular scale. This\nlimits the precision of reaction networks, but also allows fluctuation\nmeasurements which may reveal the structure and dynamics of the underlying\nbiochemical network. Here, we study non-equilibrium reaction cycles, such as\nthe mechanochemical cycle of molecular motors, the phosphorylation cycle of\ncircadian clock proteins, or the transition state cycle of enzymes.\nFluctuations in such cycles may be measured using either of two classical\ndefinitions of the randomness parameter, which we show to be equivalent in\ngeneral microscopically reversible cycles. We define a stochastic period for\nreversible cycles and present analytical solutions for its moments.\nFurthermore, we associate the two forms of the randomness parameter with the\nthermodynamic uncertainty relation, which sets limits on the timing precision\nof the cycle in terms of thermodynamic quantities. Our results should prove\nuseful also for the study of temporal fluctuations in more general networks.", "category": "physics_bio-ph" }, { "text": "Optimal elasticity of biological networks: Reinforced elastic sheets surround us in daily life, from concrete shell\nbuildings to biological structures such as the arthropod exoskeleton or the\nvenation network of dicotyledonous plant leaves. Natural structures are often\nhighly optimized through evolution and natural selection, leading to the\nbiologically and practically relevant problem of understanding and applying the\nprinciples of their design. Inspired by the hierarchically organized\nscaffolding networks found in plant leaves, here we model networks of bending\nbeams that capture the discrete and non-uniform nature of natural materials.\nUsing the principle of maximal rigidity under natural resource constraints, we\nshow that optimal discrete beam networks reproduce the structural features of\nreal leaf venation. Thus, in addition to its ability to efficiently transport\nwater and nutrients, the venation network also optimizes leaf rigidity using\nthe same hierarchical reticulated network topology. We study the phase space of\noptimal mechanical networks, providing concrete guidelines for the construction\nof elastic structures. We implement these natural design rules by fabricating\nefficient, biologically inspired metamaterials.", "category": "physics_bio-ph" }, { "text": "Enhancing the Study of Quantal Exocytotic Events: Combining Diamond\n Multi-Electrode Arrays with Amperometric PEak Analysis (APE) an Automated\n Analysis Code: MicroGraphited-Diamond-Multi Electrode Arrays ({\\mu}G-D-MEAs) can be\nsuccessfully used to reveal, in real time, quantal exocytotic events occurring\nfrom many individual neurosecretory cells and/or from many neurons within a\nnetwork. As {\\mu}G-D-MEAs arrays are patterned with up to 16 sensing\nmicroelectrodes, each of them recording large amounts of data revealing the\nexocytotic activity, the aim of this work was to support an adequate analysis\ncode to speed up the signal detection. The cutting-edge technology of\nmicroGraphited-Diamond-Multi Electrode Arrays ({\\mu}G-D-MEAs) has been\nimplemented with an automated analysis code (APE, Amperometric Peak Analysis)\ndeveloped using Matlab R2022a software to provide easy and accurate detection\nof amperometric spike parameters, including the analysis of the pre-spike foot\nthat sometimes precedes the complete fusion pore dilatation. Data have been\nacquired from cultured PC12 cells, either collecting events during spontaneous\nexocytosis or after L-DOPA incubation. Validation of the APE code was performed\nby comparing the acquired spike parameters with those obtained using Quanta\nAnalysis (Igor macro) by Mosharov et al.", "category": "physics_bio-ph" }, { "text": "Does coherence enhance transport in photosynthesis?: Recent observations of coherence in photosynthetic complexes have led to the\nquestion of whether quantum effects can occur in vivo, not under femtosecond\nlaser pulses but in incoherent sunlight and at steady state, and, if so,\nwhether the coherence explains the high exciton transfer efficiency. We\ndistinguish several types of coherence and show that although some\nphotosynthetic pathways are partially coherent processes, photosynthesis in\nnature proceeds through stationary states. This distinction allows us to rule\nout several mechanisms of transport enhancement in sunlight. In particular,\nalthough they are crucial for understanding exciton transport, neither wavelike\nmotion nor microscopic coherence, on their own, enhance the efficiency. By\ncontrast, two partially coherent mechanisms---ENAQT and supertransfer---can\nenhance transport even in sunlight and thus constitute motifs for the\noptimisation of artificial sunlight harvesting. Finally, we clarify the\nimportance of ultrafast spectroscopy in understanding incoherent processes.", "category": "physics_bio-ph" }, { "text": "Noise-induced phase transitions in neuronal networks: Using an exactly solvable cortical model of a neuronal network, we show that,\nby increasing the intensity of shot noise (flow of random spikes bombarding\nneurons), the network undergoes first- and second-order non-equilibrium phase\ntransitions. We study the nature of the transitions, bursts and avalanches of\nneuronal activity. Saddle-node and supercritical Hopf bifurcations are the\nmechanisms of emergence of sustained network oscillations. We show that the\nnetwork stimulated by shot noise behaves similar to the Morris-Lecar model of a\nbiological neuron stimulated by an applied current.", "category": "physics_bio-ph" }, { "text": "Sequencing proteins with transverse ionic transport in nanochannels: {\\it De novo} protein sequencing is essential for understanding cellular\nprocesses that govern the function of living organisms and all\npost-translational events and other sequence modifications that occur after a\nprotein has been constructed from its corresponding DNA code. By obtaining the\norder of the amino acids that composes a given protein one can then determine\nboth its secondary and tertiary structures through structure prediction, which\nis used to create models for protein aggregation diseases such as Alzheimer's\nDisease. Mass spectrometry is the current technique of choice for {\\it de novo}\nsequencing. However, because some amino acids have the same mass the sequence\ncannot be completely determined in many cases. Here, we propose a new technique\nfor {\\it de novo} protein sequencing that involves translocating a polypeptide\nthrough a synthetic nanochannel and measuring the ionic current of each amino\nacid through an intersecting {\\it perpendicular} nanochannel. To calculate the\ntransverse ionic current blockaded by a given amino acid we use a Monte Carlo\nmethod along with Ramachandran plots to determine the available flow area,\nmodified by the local density of ions obtained from molecular dynamics and the\nlocal flow velocity ratio derived from the Stokes equation. We find that the\ndistribution of ionic currents for each of the 20 proteinogenic amino acids\nencoded by eukaryotic genes is statistically distinct, showing this technique's\npotential for {\\it de novo} protein sequencing.", "category": "physics_bio-ph" }, { "text": "Synchrotron radiation microtomography of brain hemisphere and spinal\n cord of a mouse model of multiple sclerosis revealed a correlation between\n capillary dilation and clinical score: Multiple sclerosis is a neurological disorder in which the myelin sheaths of\naxons are damaged by the immune response. We report here a three-dimensional\nstructural analysis of brain and spinal cord tissues of a mouse model of\nmultiple sclerosis, known as experimental autoimmune encephalomyelitis (EAE).\nEAE-induced mice were raised with or without administration of fingolimod,\nwhich is used in the treatment of multiple sclerosis. Brains and spinal cords\ndissected from the EAE mice were lyophilized so as to reconstitute the\nintrinsic contrast of tissue elements, such as axons, in X-ray images.\nThree-dimensional structures of the brain hemispheres and spinal cords of the\nEAE mice were visualized with synchrotron radiation microtomography.\nMicrotomographic cross sections reconstructed from the X-ray images revealed\ndilation of capillary vessels and vacuolation in the spinal cord of the EAE\nmice. Vacuolation was also observed in the cerebellum, suggesting that the\nneuroinflammatory response progressed in the brain. The vessel networks and\nvacuolation lesions in the spinal cords were modelled by automatically tracing\nthe three-dimensional image in order to analyze the tissue structures\nquantitatively. The results of the analysis indicated that the distribution of\nvacuolations was not uniform but three-dimensionally localized. The mean vessel\ndiameter showed a linear correlation with the clinical score, indicating that\nvasodilation is relevant to paralysis severity in the disease model. We suggest\nthat vasodilation and vacuolation are related with neurological symptoms of\nmultiple sclerosis.", "category": "physics_bio-ph" }, { "text": "Characterization of the Frictional Response of Squamata Shed Skin in\n Comparison to Human skin: Deterministic surfaces are constructs of which profile, topography and\ntextures are integral to the function of the system they enclose. They are\ndesigned to yield a predetermined rubbing response. Developing such entities\nrelies on controlling the structure of the rubbing interface so that, not only\nthe surface is of optimized topography, but also is able to self-adjust its\nbehavior according to the evolution of sliding conditions. Inspirations for\nsuch designs are frequently encountered in natural species. In particular, and\nfrom a tribological point of view, Squamate Reptiles, offer diverse examples\nwhere surface texturing, submicron and nano-scale features, achieves frictional\nregulation. In this paper, we study the frictional response of shed skin\nobtained from a Python regius snake. The study employed a specially designed\ntribo-acoustic probe capable of measuring the coefficient of friction and\ndetecting the acoustical behavior of the skin in vivo. The results confirm the\nanisotropy of the frictional response of snakes. It is found that the\ncoefficient of friction depends on the direction of sliding: the value in\nforward motion is lower than that in the backward direction. Diagonal and side\nwinding motion induces a different value of the friction coefficient. We\ndiscuss the origin of such a phenomenon in relation to surface texturing and\nstudy the energy constraints, implied by anisotropic friction, on the motion of\nthe reptile and to establish a reference for comprehending the frictional\nresponse we draw a comparison to the friction of human skin.", "category": "physics_bio-ph" }, { "text": "Tunable Oscillations in the Purkinje Neuron: In this paper, we study the dynamics of slow oscillations in Purkinje neurons\nin vitro, and derive a strong association with a forced parametric oscillator\nmodel. We demonstrate the precise rhythmicity of the oscillations in Purkinje\nneurons, as well as a dynamic tunability of this oscillation using a\nphoto-switchable compound. We show that this slow oscillation can be induced in\nevery Purkinje neuron, having periods ranging between 10-25 seconds. Starting\nfrom a Hodgkin-Huxley model, we also demonstrate that this oscillation can be\nexternally modulated, and that the neurons will return to their intrinsic\nfiring frequency after the forced oscillation is concluded. These results\nsignify an additional functional role of tunable oscillations within the\ncerebellum, as well as a dynamic control of a time scale in the brain in the\nrange of seconds.", "category": "physics_bio-ph" }, { "text": "Experimental evidence for a power law in electroencephalographic\n $\u03b1$-wave dynamics: We perform an experimental study of the time behavior of the $\\alpha$-wave\nevents occuring in human electroencephalographic signals. We find that the\nfraction of the time spent in an $\\alpha$-burst of time size $\\tau$ exhibits a\nscaling behavior as a function of $\\tau$. The corresponding exponent is equal\nto 1.75$\\pm$0.13. We therefore point out the existence of a new power law\nappearing in physiology. Furhtermore, we show that our experimental result may\nhave a possible explanation within a class of Self-Organized Critical (SOC)\nmodels recently proposed by Boettcher and Paczuski. In particular, one of these\nmodels, when properly re-interpreted, seems to be consistent both with our\nresult and a commonly accepted physiological description of the possible origin\nof $\\alpha$-wave events.", "category": "physics_bio-ph" }, { "text": "Ultrahigh-Frequency Wireless MEMS QCM Biosensor for Direct Label-Free\n Detection of Biomarkers in a Large Amount of Contaminants: Label-free biosensors, including conventional quartz-crystal-microbalance\n(QCM) biosensor, are seriously affected by nonspecific adsorption of\ncontaminants involved in analyte solution, and it is exceptionally difficult to\nextract the sensor responses caused only by the targets. In this study, we\nreveal that this difficulty can be overcome with an ultrahigh-frequency\nwireless QCM biosensor. The sensitivity of a QCM biosensor dramatically\nimproves by thinning the quartz resonator, which also makes the resonance\nfrequency higher, causing high-speed surface movement. Contaminants weakly\n(nonspecifically) interact with the quartz surface, and they fail to follow the\nfast surface movement and cannot be detected as the loaded mass. The targets\nare, however, tightly captured by the receptor proteins immobilized on the\nsurface, and they can move with the surface, contributing to the loaded mass\nand decreasing the resonant frequency. We develop a MEMS QCM biosensor, in\nwhich an AT-cut quartz resonator of 26 {\\mu}m thick is packaged without fixing,\nand demonstrate this phenomenon by comparing the frequency changes of\nfundamental (about 64 MHz) and ninth (about 576 MHz) modes. At\nultrahigh-frequency operation with the ninth mode, the sensor response is\nindependent of the amount of impurity proteins, and the binding affinity is\nunchanged. We then applied this method for the label-free and sandwich-free\ndirect detection of C-reactive protein (CRP) in serum, and confirmed its\napplicability.", "category": "physics_bio-ph" }, { "text": "Phase field model for phagocytosis dynamics: The basic process of the innate immune system when phagocyte (white blood\ncell) engulf or swallow a target particle (bacterium or dead cell), is called\nphagocytosis. We apply the phase field approach in the spirit of [1], that\ncouples the order parameter $u$ with 3D polarization (orientation) vector field\n$\\textbf{P}$ of the actin network of the phagocyte cytoskeleton. We derive a\nsingle closed scalar integro-differential equation governing the 3D phagocyte\nmembrane dynamics during bead engulfment, which includes the normal velocity of\nthe membrane, curvature, volume relaxation rate, a function determined by the\nmolecular effects of the subcell level, and the adhesion effect of the\nmotionless rigid spherical bead. This equation is easily solved numerically.\nThe simulation manifests the pedestal and the cup phases but not the final\ncomplete bead internalization.", "category": "physics_bio-ph" }, { "text": "Accounting for the thickness effect in dynamic spherical indentation of\n a viscoelastic layer: Application to non-destructive testing of articular\n cartilage: In recent years, dynamic indentation tests have been shown to be useful both\nin identification of mechanical properties of biological tissues (such as\narticular cartilage) and assessing their viability. We consider frictionless\nflat-ended and spherical sinusoidally-driven indentation tests utilizing\ndisplacement-controlled loading protocol. Articular cartilage tissue is modeled\nas a viscoelastic material with a time-independent Poisson's ratio. We study\nthe dynamic indentation stiffness with the aim of formulating criteria for\nevaluation the quality of articular cartilage in order to be able to\ndiscriminate its degenerative state. In particular, evaluating the dynamic\nindentation stiffness at the turning point of the flat-ended indentation test,\nwe introduce the so-called incomplete storage modulus. Considering the time\ndifference between the time moments when the dynamic stiffness vanishes\n(contact force reaches its maximum) and the dynamic stiffness becomes infinite\n(indenter displacement reaches its maximum), we introduce the so-called\nincomplete loss angle. Analogous quantities can be introduced in the spherical\nsinusoidally-driven indentation test, however, to account for the thickness\neffect, a special approach is required. We apply an asymptotic modeling\napproach for analyzing and interpreting the results of the dynamic spherical\nindentation test in terms of the geometrical parameter of the indenter and\nviscoelastic characteristics of the material. Some implications to\nnon-destructive indentation diagnostics of cartilage degeneration are\ndiscussed.", "category": "physics_bio-ph" }, { "text": "OpenRBC: A Fast Simulator of Red Blood Cells at Protein Resolution: We present OpenRBC, a coarse-grained molecular dynamics code, which is\ncapable of performing an unprecedented in silico experiment --- simulating an\nentire mammal red blood cell lipid bilayer and cytoskeleton as modeled by 4\nmillion mesoscopic particles --- using a single shared memory commodity\nworkstation. To achieve this, we invented an adaptive spatial-searching\nalgorithm to accelerate the computation of short-range pairwise interactions in\nan extremely sparse 3D space. The algorithm is based on a Voronoi partitioning\nof the point cloud of coarse-grained particles, and is continuously updated\nover the course of the simulation. The algorithm enables the construction of\nthe key spatial searching data structure in our code, i.e. a lattice-free cell\nlist, with a time and space cost linearly proportional to the number of\nparticles in the system. The position and shape of the cells also adapt\nautomatically to the local density and curvature. The code implements OpenMP\nparallelization and scales to hundreds of hardware threads. It outperforms a\nlegacy simulator by almost an order of magnitude in time-to-solution and more\nthan 40 times in problem size, thus providing a new platform for probing the\nbiomechanics of red blood cells.", "category": "physics_bio-ph" }, { "text": "Evolved interactions stabilize many coexisting phases in multicomponent\n liquids: Phase separation has emerged as an essential concept for the spatial\norganization inside biological cells. However, despite the clear relevance to\nvirtually all physiological functions, we understand surprisingly little about\nwhat phases form in a system of many interacting components, like in cells.\nHere, we introduce a new numerical method based on physical relaxation dynamics\nto study the coexisting phases in such systems. We use our approach to optimize\ninteractions between components, similar to how evolution might have optimized\nthe interactions of proteins. These evolved interactions robustly lead to a\ndefined number of phases, despite substantial uncertainties in the initial\ncomposition, while random or designed interactions perform much worse.\nMoreover, the optimized interactions are robust to perturbations and they allow\nfast adaption to new target phase counts. We thus show that genetically encoded\ninteractions of proteins provide versatile control of phase behavior. The\nphases forming in our system are also a concrete example of a robust emergent\nproperty that does not rely on fine-tuning the parameters of individual\nconstituents.", "category": "physics_bio-ph" }, { "text": "Maximum likelihood analysis of non-equilibrium solution-based\n single-molecule FRET data: Measuring the F\\\"{o}rster resonance energy transfer (FRET) efficiency of\nfreely diffusing single molecules provides information about the sampled\nconformational states of the molecules. Under equilibrium conditions, the\ndistribution of the conformational states is independent of time, whereas it\ncan vary over time under non-equilibrium conditions. In this work, we consider\nthe problem of parameter inference on non-equilibrium solution-based\nsingle-molecule FRET data. With a non-equilibrium model for the conformational\ndynamics and a model for the conformation-dependent FRET efficiency\ndistribution, the likelihood function could be constructed. The model\nparameters, such as the rate constants of the non-equilibrium conformational\ndynamics model and the average FRET efficiencies of the different\nconformational states, have been estimated from the data by maximizing the\nappropriate likelihood function via the Expectation-Maximization algorithm. We\nillustrate the likelihood method for a few simple non-equilibrium models and\nvalidated the method by simulations. The likelihood method could be applied to\nstudy protein folding, macromolecular complex formation, protein conformational\ndynamics and other non-equilibrium processes at the single-molecule level and\nin solution.", "category": "physics_bio-ph" }, { "text": "Morphology and size of bacterial colonies control anoxic\n microenvironment formation in porous media: Anaerobic processes (e.g., methanogenesis and fermentation) largely\ncontribute to element cycling and natural contaminant attenuation/mobilization,\neven in well-oxygenated porous environments, such as shallow aquifers. This\nparadox is commonly explained by the occurrence of small-scale anoxic\nmicroenvironments generated by the coupling of bacterial respiration and the\nheterogeneous oxygen (O2) transport by porewater. Such microenvironments allow\nfacultatively and obligately anaerobic bacteria to proliferate in oxic\nenvironments. Microenvironment dynamics are still poorly understood due to the\nchallenge of directly observing biomass and O2 distributions at the microscale\nwithin an opaque sediment and soil matrix. To overcome these limitations, we\nintegrated a microfluidic device with transparent O2 planar optical sensors to\nmeasure the temporal behavior of dissolved O2 concentrations and biomass\ndistributions with time-lapse video-microscopy. Our results reveal that\nbacterial colony morphology, which is highly variable in flowing porous\nsystems, controls the formation of anoxic microenvironments. We rationalize our\nobservations through a colony-scale Damkohler number comparing dissolved O2\ndiffusion and bacterial O2 uptake rate. Our Damkholer number enables predicting\nthe pore space occupied by anoxic microenvironments in our system, and, given\nthe bacterial organization, it can be applied to 3D porous systems.", "category": "physics_bio-ph" }, { "text": "Asymmetric spreading in highly advective, disordered environments: Spreading of bacteria in a highly advective, disordered environment is\nexamined. Predictions of super-diffusive spreading for a simplified\nreaction-diffusion equation are tested. Concentration profiles display\nanomalous growth and super-diffusive spreading. A perturbation analysis yields\na crossover time between diffusive and super-diffusive behavior. The time's\ndependence on the convection velocity and disorder is tested. Like the\nsimplified equation, the full linear reaction-diffusion equation displays\nsuper-diffusive spreading perpendicular to the convection. However, for mean\npositive growth rates the full nonlinear reaction-diffusion equation produces\nsymmetric spreading with a Fisher wavefront, whereas net negative growth rates\ncause an asymmetry, with a slower wavefront velocity perpendicular to the\nconvection.", "category": "physics_bio-ph" }, { "text": "Multiscale approach to the physics of radiation damage with ions: The multiscale approach to the assessment of biodamage resulting upon\nirradiation of biological media with ions is reviewed, explained and compared\nto other approaches. The processes of ion propagation in the medium concurrent\nwith ionization and excitation of molecules, transport of secondary products,\ndynamics of the medium, and biological damage take place on a number of\ndifferent temporal, spatial and energy scales. The multiscale approach, a\nphysical phenomenon-based analysis of the scenario that leads to radiation\ndamage, has been designed to consider all relevant effects on a variety of\nscales and develop an approach to the quantitative assessment of biological\ndamage as a result of irradiation with ions. This paper explains the scenario\nof radiation damage with ions, overviews its major parts, and applies the\nmultiscale approach to different experimental conditions. On the basis of this\nexperience, the recipe for application of the multiscale approach is\nformulated. The recipe leads to the calculation of relative biological\neffectiveness.", "category": "physics_bio-ph" }, { "text": "Nonlinear dynamics of the mammalian inner ear: A simple nonlinear transmission-line model of the cochlea with longitudinal\ncoupling is introduced that can reproduce Basilar membrane response and neural\ntuning in the chinchilla. It is found that the middle ear has little effect on\ncochlear resonances, and hence conclude that the theory of coherent reflections\nis not applicable to the model. The model also provides an explanation of the\nemergence of spontaneous otoacoustic emissions (SOAEs). It is argued that SOAEs\narise from Hopf bifurcations of the transmission-line model and not from\nlocalized instabilities. The paper shows that emissions can become chaotic,\nintermittent and fragile to perturbations.", "category": "physics_bio-ph" }, { "text": "A steering mechanism for phototaxis in Chlamydomonas: Chlamydomonas shows both positive and negative phototaxis. It has a single\neyespot near its equator and as the cell rotates during forward motion the\nlight signal received by the eyespot varies. We use a simple mechanical model\nof Chlamydomonas that couples the flagellar beat pattern to the light intensity\nat the eyespot to demonstrate a mechanism for phototactic steering that is\nconsistent with observations. The direction of phototaxis is controlled by a\nparameter in our model and the steering mechanism is robust to noise. Our model\nshows switching between directed phototaxis when the light is on and\nrun-and-tumble behaviour in the dark.", "category": "physics_bio-ph" }, { "text": "Weak tension accelerates hybridization and dehybridization of short\n oligonucleotides: The hybridization and dehybridization of DNA subject to tension is relevant\nto fundamental genetic processes and to the design of DNA-based mechanobiology\nassays. While strong tension accelerates DNA melting and decelerates DNA\nannealing, the effects of tension weaker than 5 pN are less clear. In this\nstudy, we developed a DNA bow assay, which uses the bending rigidity of\ndouble-stranded DNA (dsDNA) to exert weak tension on a single-stranded DNA\n(ssDNA) target in the range of 2 pN to 6 pN. Combining this assay with\nsingle-molecule FRET, we measured the hybridization and dehybridization\nkinetics between a 15 nt ssDNA under tension and a 8-9 nt oligo, and found that\nboth the hybridization and dehybridization rates monotonically increase with\ntension for various nucleotide sequences tested. These findings suggest that\nthe nucleated duplex in its transition state is more extended than the pure\ndsDNA or ssDNA counterpart. Our simulations using the coarse-grained oxDNA2\nmodel indicate that the increased extension of the transition state is due to\nexclusion interactions between unpaired ssDNA regions in close proximity to one\nanother. This study highlights an example where the ideal worm-like chain\nmodels fail to explain the kinetic behavior of DNA in the low force regime.", "category": "physics_bio-ph" }, { "text": "Lognormal distribution of firing time and rate from a single neuron?: Even a single neuron may be able to produce significant lognormal features in\nits firing statistics due to noise in the charging ion current. A mathematical\nscheme introduced in advanced nanotechnology is relevant for the analysis of\nthis mechanism in the simplest case, the integrate-and-fire model with white\nnoise in the charging ion current.", "category": "physics_bio-ph" }, { "text": "Spectroscopic investigation of local mechanical impedance of living\n cells: The mechanical properties of PC12 living cells have been studied at the\nnanoscale with a Force Feedback Microscope using two experimental approaches.\nFirstly, the local mechanical impedance of the cell membrane has been mapped\nsimultaneously to the cell morphology at constant force. As the force of the\ninteraction is gradually increased, we observed the appearance of the\nsub-membrane cytoskeleton. We shall compare the results obtained with this\nmethod with the measurement of other existing techniques. Secondly, a\nspectroscopic investigation has been performed varying the indentation of the\ntip in the cell membrane and consequently the force applied on it. In contrast\nwith conventional dynamic atomic force microscopy techniques, here the small\noscillation amplitude of the tip is not necessarily imposed at the cantilever\nfirst eigenmode. This allows the user to arbitrarily choose the excitation\nfrequency in developing spectroscopic AFM techniques. The mechanical response\nof the PC12 cell membrane is found to be frequency dependent in the 1 kHz - 10\nkHz range. The damping coefficient is reproducibly observed to decrease when\nthe excitation frequency is increased.", "category": "physics_bio-ph" }, { "text": "Scaling behavior of non-equilibrium measures in internally driven\n elastic assemblies: Detecting and quantifying non-equilibrium activity is essential for studying\ninternally driven assemblies, including synthetic active matter and complex\nliving systems such as cells or tissue. We discuss a non-invasive approach of\nmeasuring non-equilibrium behavior based on the breaking of detailed balance.\nWe focus on \"cycling frequencies\" - the average frequency with which the\ntrajectories of pairs of degrees of freedom revolve in phase space, and explain\ntheir connection with other non-equilibrium measures, including the area\nenclosing rate and the entropy production rate. We test our approach on simple\ntoy-models comprised of elastic networks immersed in a viscous fluid with\nsite-dependent internal driving. We prove both numerically and analytically\nthat the cycling frequencies obey a power-law as a function of distance between\nthe tracked degrees of freedom. Importantly, the behavior of the cycling\nfrequencies contains information about the dimensionality of the system and the\namplitude of active noise. The mapping we use in our analytical approach thus\noffers a convenient framework for predicting the behavior of two-point\nnon-equilibrium measures for a given activity distribution in the network.", "category": "physics_bio-ph" }, { "text": "Motor-Driven Bacterial Flagella and Buckling Instabilities: Many types of bacteria swim by rotating a bundle of helical filaments also\ncalled flagella. Each filament is driven by a rotary motor and a very flexible\nhook transmits the motor torque to the filament. We model it by discretizing\nKirchhoff's elastic-rod theory and develop a coarse-grained approach for\ndriving the helical filament by a motor torque. A rotating flagellum generates\na thrust force, which pushes the cell body forward and which increases with the\nmotor torque. We fix the rotating flagellum in space and show that it buckles\nunder the thrust force at a critical motor torque. Buckling becomes visible as\na supercritical Hopf bifurcation in the thrust force. A second buckling\ntransition occurs at an even higher motor torque. We attach the flagellum to a\nspherical cell body and also observe the first buckling transition during\nlocomotion. By changing the size of the cell body, we vary the necessary thrust\nforce and thereby obtain a characteristic relation between the critical thrust\nforce and motor torque. We present a sophisticated analytical model for the\nbuckling transition based on a helical rod which quantitatively reproduces the\ncritical force-torque relation. Real values for motor torque, cell body size,\nand the geometry of the helical filament suggest that buckling should occur in\nsingle bacterial flagella. We also find that the orientation of pulling\nflagella along the driving torque is not stable and comment on the biological\nrelevance for marine bacteria.", "category": "physics_bio-ph" }, { "text": "A minimal model for structure, dynamics, and tension of monolayered cell\n colonies: The motion of cells in tissues is an ubiquitous phenomenon. In particular, in\nmonolayered cell colonies in vitro, pronounced collective behavior with\nswirl-like motion has been observed deep within a cell colony, while at the\nsame time, the colony remains cohesive, with not a single cell escaping at the\nedge. Thus, the colony displays liquid-like properties inside, in coexistence\nwith a cell-free \"vacuum\" outside. How can adhesion be strong enough to keep\ncells together, while at the same time not jam the system in a glassy state?\nWhat kind of minimal model can describe such a behavior? Which other signatures\nof activity arise from the internal fluidity? We propose a novel active\nBrownian particle model with attraction, in which the interaction potential has\na broad minimum to give particles enough wiggling space to be collectively in\nthe fluid state. We demonstrate that for moderate propulsion, this model can\ngenerate the fluid-vacuum coexistence described above. In addition, the\ncombination of the fluid nature of the colony with cohesion leads to preferred\norientation of the cell polarity, pointing outward, at the edge, which in turn\ngives rise to a tensile stress in the colony -- as observed experimentally for\nepithelial sheets. For stronger propulsion, collective detachment of cell\nclusters is predicted. Further addition of an alignment preference of cell\npolarity and velocity direction results in enhanced coordinated, swirl-like\nmotion, increased tensile stress and cell-cluster detachment.", "category": "physics_bio-ph" }, { "text": "Novel Phonoreceptive Mechanism of the Cochlear for Low-frequency Sound: Because the cochlear is very small and complex, vibration data of the whole\nbasement membrane are not yet available from existing experiments, To address\nthis question, this work technically adopts the mathematical and biological\nmethods to establish a theoretical analytical model of the Spiral cochlear ,\ncombined with medical and modern light source imaging experimental data. In\naddition, a numerical model of a real human ear is also established. By\nperforming numerous calculations, the results reproduce the known travelling\nwave vibration of basement membrane. Meanwhile, an exciting finding that\nrevealing a new vibration mode is obtained. More importantly, this newly\ndiscovered model intrinsically explain many experimental observations that\ncannot be explained by travelling wave theory, which solves a long standing\nvarious queries to travelling wave vibration among researchers. These results\nnot only complement vibration data that are inaccessible through experiments\nbut also reveal a new hearing mechanism.", "category": "physics_bio-ph" }, { "text": "Free energy landscape and characteristic forces for the initiation of\n DNA unzipping: DNA unzipping, the separation of its double helix into single strands, is\ncrucial in modulating a host of genetic processes. Although the large-scale\nseparation of double-stranded DNA has been studied with a variety of\ntheoretical and experimental techniques, the minute details of the very first\nsteps of unzipping are still unclear. Here, we use atomistic molecular dynamics\n(MD) simulations, coarse-grained simulations and a statistical-mechanical model\nto study the initiation of DNA unzipping by an external force. The calculation\nof the potential of mean force profiles for the initial separation of the first\nfew terminal base pairs in a DNA oligomer reveal that forces ranging between\n130 and 230 pN are needed to disrupt the first base pair, values of an order of\nmagnitude larger than those needed to disrupt base pairs in partially unzipped\nDNA. The force peak has an \"echo,\" of approximately 50 pN, at the distance that\nunzips the second base pair. We show that the high peak needed to initiate\nunzipping derives from a free energy basin that is distinct from the basins of\nsubsequent base pairs because of entropic contributions and we highlight the\nmicroscopic origin of the peak. Our results suggest a new window of exploration\nfor single molecule experiments.", "category": "physics_bio-ph" }, { "text": "Kaleidoscope Eyes: Microstructure and Optical Performance of Chiton\n Ocelli: The chiton Acanthopleura granulata uses aragonitic lenses embedded in its\nshell to focus light onto photoreceptors. Because aragonite is biaxially\nbirefringent, the microstructure of the lens greatly impacts the optical\nperformance. In addition, the chiton lives in the intertidal, so lenses\nexperience two environments with different refractive indices: air and water.\nUsing EBSD, we find that the lens is polycrystalline and contains curved grain\nboundaries. A combination of large, twinned grains and nanotwins ensure that\nthe aragonitic <001> axis is consistent across the lens. However, the\norientation of the <001> axis relative to the shell varies between lenses. Ray\ntracing simulations predict the optical performance of lenses of various\nmicrostructures in wet and dry environments. Though twinning helps to limit\nbirefringence-induced aberrations, variations in the orientation of the <001>\naxis between lenses lead to variations in focal lengths between lenses and\ncause image doubling in some lenses. As such, the birefringence of aragonite\ndoes not help the lens to transmit focused images in both air and water.", "category": "physics_bio-ph" }, { "text": "Exact solution for the Anisotropic Ornstein-Uhlenbeck Process: Active Matter models commonly consider particles with overdamped dynamics\nsubject to a force (speed) with constant modulus and random direction. Some\nmodels include also random noise in particle displacement (Wiener process)\nresulting in a diffusive motion at short time scales. On the other hand,\nOrnstein-Uhlenbeck processes consider Langevin dynamics for the particle\nvelocity and predict a motion that is not diffusive at short time scales.\nHowever, experiments show that migrating cells may present a varying speed as\nwell as a short-time diffusive behavior. While Ornstein-Uhlenbeck processes can\ndescribe the varying speed, Active Mater models can explain the short-time\ndiffusive behavior. Isotropic models cannot explain both: short-time diffusion\nrenders instantaneous velocity ill-defined, hence impeding dynamical equations\nthat consider velocity time-derivatives. On the other hand, both models apply\nfor migrating biological cells and must, in some limit, yield the same\nobservable predictions. Here we propose and analytically solve an Anisotropic\nOrnstein-Uhlenbeck process that considers polarized particles, with a Langevin\ndynamics for the particle movement in the polarization direction while\nfollowing a Wiener process for displacement in the orthogonal direction. Our\ncharacterization provides a theoretically robust way to compare movement in\ndimensionless simulations to movement in dimensionful experiments, besides\nproposing a procedure to deal with inevitable finite precision effects in\nexperiments or simulations.", "category": "physics_bio-ph" }, { "text": "Optical tweezers approaches for probing multiscale protein mechanics and\n assembly: Multi-step assembly of individual protein building blocks is key to the\nformation of essential higher-order structures inside and outside of cells.\nOptical tweezers is a technique well suited to investigate the mechanics and\ndynamics of these structures at a variety of size scales. In this mini-review,\nwe highlight experiments that have used optical tweezers to investigate protein\nassembly and mechanics, with a focus on the extracellular matrix protein\ncollagen. These examples demonstrate how optical tweezers can be used to study\nmechanics across length scales, ranging from the single-molecule level to\nfibrils to protein networks. We discuss challenges in experimental design and\ninterpretation, opportunities for integration with other experimental\nmodalities, and applications of optical tweezers to current questions in\nprotein mechanics and assembly.", "category": "physics_bio-ph" }, { "text": "Melting of genomic DNA: predictive modeling by nonlinear lattice\n dynamics: The melting behavior of long, heterogeneous DNA chains is examined within the\nframework of the nonlinear lattice dynamics based Peyrard-Bishop-Dauxois (PBD)\nmodel. Data for the pBR322 plasmid and the complete T7 phage have been used to\nobtain model fits and determine parameter dependence on salt content. Melting\ncurves predicted for the complete fd phage and the Y1 and Y2 fragments of the\n$\\phi$X174 phage without any adjustable parameters are in good agreement with\nexperiment. The calculated probabilities for single base-pair opening are\nconsistent with values obtained from imino proton exchange experiments.", "category": "physics_bio-ph" }, { "text": "Interplay between HIV/AIDS Epidemics and Demographic Structures Based on\n Sexual Contact Networks: In this article, we propose a network spread model for HIV epidemics, wherein\neach individual is represented by a node of the transmission network and the\nedges are the connections between individuals along which the infection may\nspread. The sexual activity of each individual, measured by its degree, is not\nhomogeneous but obeys a power-law distribution. Due to the heterogeneity of\nactivity, the infection can persistently exist at a very low prevalence, which\nhas been observed in real data but can not be illuminated by previous models\nwith homogeneous mixing hypothesis. Furthermore, the model displays a clear\npicture of hierarchical spread: In the early stage the infection is adhered to\nthese high-risk persons, and then, diffuses toward low-risk population. The\nprediction results show that the development of epidemics can be roughly\ncategorized into three patterns for different countries, and the pattern of a\ngiven country is mainly determined by the average sex-activity and transmission\nprobability per sexual partner. In most cases, the effect of HIV epidemics on\ndemographic structure is very small. However, for some extremely countries,\nlike Botswana, the number of sex-active people can be depressed to nearly a\nhalf by AIDS.", "category": "physics_bio-ph" }, { "text": "Dynamic fitness landscapes: Expansions for small mutation rates: We study the evolution of asexual microorganisms with small mutation rate in\nfluctuating environments, and develop techniques that allow us to expand the\nformal solution of the evolution equations to first order in the mutation rate.\nOur method can be applied to both discrete time and continuous time systems.\nWhile the behavior of continuous time systems is dominated by the average\nfitness landscape for small mutation rates, in discrete time systems it is\ninstead the geometric mean fitness that determines the system's properties. In\nboth cases, we find that in situations in which the arithmetic (resp.\ngeometric) mean of the fitness landscape is degenerate, regions in which the\nfitness fluctuates around the mean value present a selective advantage over\nregions in which the fitness stays at the mean. This effect is caused by the\nvanishing genetic diffusion at low mutation rates. In the absence of strong\ndiffusion, a population can stay close to a fluctuating peak when the peak's\nheight is below average, and take advantage of the peak when its height is\nabove average.", "category": "physics_bio-ph" }, { "text": "A library-based Monte Carlo technique enables rapid equilibrium sampling\n of a protein model with atomistic components: There is significant interest in rapid protein simulations because of the\ntime-scale limitations of all-atom methods. Exploiting the low cost and great\navailability of computer memory, we report a Monte Carlo technique for\nincorporating fully flexible atomistic protein components (e.g., peptide\nplanes) into protein models without compromising sampling speed or statistical\nrigor. Building on existing approximate methods (e.g., Rosetta), the technique\nuses pre-generated statistical libraries of all-atom components which are\nswapped with the corresponding protein components during a simulation. The\nsimple model we study consists of the three all-atom backbone residues -- Ala,\nGly, and Pro -- with structure-based (Go-like) interactions. For the five\ndifferent proteins considered in this study, LBMC can generate at least 30\nstatistically independent configurations in about a month of single CPU time.\nMinimal additional cost is required to add residue-specific interactions.", "category": "physics_bio-ph" }, { "text": "Mechanism for collective cell alignment in Myxococcus xanthus bacteria: Myxococcus xanthus cells self-organize into aligned groups, clusters, at\nvarious stages of their lifecycle. Formation of these clusters is crucial for\nthe complex dynamic multi-cellular behavior of these bacteria. However, the\nmechanism underlying the cell alignment and clustering is not fully understood.\nMotivated by studies of clustering in self-propelled rods, we hypothesized that\nM. xanthus cells can align and form clusters through pure mechanical\ninteractions among cells and between cells and substrate. We test this\nhypothesis using an agent-based simulation framework in which each agent is\nbased on the biophysical model of an individual M. xanthus cell. We show that\nmodel agents, under realistic cell flexibility values, can align and form cell\nclusters but only when periodic reversals of cell directions are suppressed.\nHowever, by extending our model to introduce the observed ability of cells to\ndeposit and follow slime trails, we show that effective trail-following leads\nto clusters in reversing cells. Furthermore, we conclude that mechanical cell\nalignment combined with slime-trail-following is sufficient to explain the\ndistinct clustering behaviors observed for wild-type and non-reversing M.\nxanthus mutants in recent experiments. Our results are robust to variation in\nmodel parameters, match the experimentally observed trends and can be applied\nto understand surface motility patterns of other bacterial species.", "category": "physics_bio-ph" }, { "text": "Demographic noise and resilience in a semi-arid ecosystem model: The scarcity of water characterising drylands forces vegetation to adopt\nappropriate survival strategies. Some of these generate water-vegetation\nfeedback mechanisms that can lead to spatial self-organisation of vegetation,\nas it has been shown with models representing plants by a density of biomass,\nvarying continuously in time and space. However, although plants are usually\nquite plastic they also display discrete qualities and stochastic behaviour.\nThese features may give rise to demographic noise, which in certain cases can\ninfluence the qualitative dynamics of ecosystem models. In the present work we\nexplore the effects of demographic noise on the resilience of a model semi-arid\necosystem. We introduce a spatial stochastic eco-hydrological hybrid model in\nwhich plants are modelled as discrete entities subject to stochastic dynamical\nrules, while the dynamics of surface and soil water are described by continuous\nvariables. The model has a deterministic approximation very similar to previous\ncontinuous models of arid and semi-arid ecosystems. By means of numerical\nsimulations we show that demographic noise can have important effects on the\nextinction and recovery dynamics of the system. In particular we find that the\nstochastic model escapes extinction under a wide range of conditions for which\nthe corresponding deterministic approximation predicts absorption into desert\nstates.", "category": "physics_bio-ph" }, { "text": "Orbiting of bacteria around micrometer-sized particles entrapping\n shallow tents of fluids: Hydrodynamics and confinement dominate bacterial mobility near solid or\nair-water boundaries, causing flagellated bacteria to move in circular\ntrajectories. This phenomenon results from the counter-rotation between the\nbacterial body and flagella and lateral drags on them in opposite directions\ndue to their proximity to the boundaries. Numerous experimental techniques have\nbeen developed to confine and maneuver motile bacteria. Here, we report\nobservations on Escherichia coli and Enterobacter sp. when they are confined\nwithin a thin layer of water around dispersed micrometer-sized particles\nsprinkled over a semi-solid agar gel. In this setting, the flagellated bacteria\norbit around the dispersed particles akin to planetary systems. The liquid\nlayer is shaped like a shallow tent with its height at the center set by the\nseeding particle and the meniscus profile set by the strong surface tension of\nwater. The tent-shaped constraint and the left handedness of the flagellar\nfilaments result in exclusively clockwise circular trajectories. The thin fluid\nlayer is resilient due to a balance between evaporation and reinforcing fluid\npumped out of the agar. The latter is driven by the Laplace pressure caused by\nthe curved meniscus. This novel mechanism to entrap bacteria within a minimal\nvolume of fluid is relevant to near surface bacterial accumulation, adhesion,\nbiofilm growth, development of bio-microdevices, and cleansing hygiene.", "category": "physics_bio-ph" }, { "text": "Length control of long cell protrusions: rulers, timers and transport: A living cell uses long tubular appendages for locomotion and sensory\npurposes. Hence, assembling and maintaining a protrusion of correct length is\ncrucial for its survival and overall performance. Usually the protrusions lack\nthe machinery for the synthesis of building blocks and imports them from the\ncell body. What are the unique features of the transport logistics which\nfacilitate the exchange of these building blocks between the cell and the\nprotrusion? What kind of `rulers' and `timers' does the cell use for\nconstructing its appendages of correct length on time? How do the multiple\nappendages coordinate and communicate among themselves during different stages\nof their existence? How frequently do the fluctuations drive the length of\nthese dynamic protrusions out of the acceptable bounds? These questions are\naddressed from a broad perspective in this review which is organized in three\nparts. In part-I the list of all known cell protrusions is followed by a\ncomprehensive list of the mechanisms of length control of cell protrusions\nreported in the literature. We review not only the dynamics of the genesis of\nthe protrusions, but also their resorption and regrowth as well as regeneration\nafter amputation. As a case study in part-II, the specific cell protrusion that\nhas been discussed in detail is eukaryotic flagellum (also known as cilium);\nthis choice was dictated by the fact that flagellar length control mechanisms\nhave been studied most extensively over more than half a century in cells with\ntwo or more flagella. Although limited in scope, brief discussions on a few\nnon-flagellar cell protrusions in part-III of this review is intended to\nprovide a glimpse of the uncharted territories and challenging frontiers of\nresearch on subcellular length control phenomena that awaits vigorous\ninvestigations.", "category": "physics_bio-ph" }, { "text": "Single-molecule force spectroscopy reveals structural differences of\n heparan sulfate chains during binding to vitronectin: The syndecans represent an ongoing research field focused on their regulatory\nroles in normal and pathological conditions. Syndecan's role in cancer\nprogression becomes well-documented, implicating their importance in diagnosis\nand even proposing various cancer potential treatments. Thus, the\ncharacterization of the unbinding properties at the single molecules level will\nappeal to their use as targets for therapeutics. In our study, syndecan-1 and\nsyndecan-4 were measured during the interaction with the vitronectin HEP II\nbinding site. Our findings show that syndecans are calcium ion-dependent\nmolecules that reveal distinct, unbinding properties indicating the alterations\nin heparin sulfate chain structure, possibly in the chain sequence or sulfation\npattern. In that way, we suppose that HS chain affinity to ECM proteins may\ngovern cancer invasion by altering syndecan ability to interact with\ncancer-related receptors present in the tumor microenvironment, thereby\npromoting the activation of various signaling cascades regulating tumor cell\nbehavior.", "category": "physics_bio-ph" }, { "text": "Cross-inhibition leads to group consensus despite the presence of\n strongly opinionated minorities and asocial behaviour: Strongly opinionated minorities can have a dramatic impact on the opinion\ndynamics of a large population. Two factions of inflexible minorities,\npolarised into two competing opinions, could lead the entire population to\npersistent indecision. Equivalently, populations can remain undecided when\nindividuals sporadically change their opinion based on individual information\nrather than social information. Our analysis compares the cross-inhibition\nmodel with the voter model for decisions between equally good alternatives, and\nwith the weighted voter model for decisions among alternatives characterised by\ndifferent qualities. Here we show that cross-inhibition, differently from the\nother two models, is a simple mechanism, ubiquitous in collective biological\nsystems, that allows the population to reach a stable majority for one\nalternative even in the presence of asocial behaviour. The results predicted by\nthe mean-field models are confirmed by experiments with swarms of 100 locally\ninteracting robots. This work suggests an answer to the longstanding question\nof why inhibitory signals are widespread in natural systems of collective\ndecision making, and, at the same time, it proposes an efficient mechanism for\ndesigning resilient swarms of minimalistic robots.", "category": "physics_bio-ph" }, { "text": "An In-Silico Study on Integrated Mechanisms of Mechano-Electric Coupling\n in Ischaemic Arrhythmogenesis: Heterogeneous mechanical dyskinesis during acute myocardial ischaemia is\nthought to contribute to arrhythmogenic alterations to cardiac\nelectrophysiology. Various forms of mechano-electric coupling (MEC) mechanisms\nhave been suggested to contribute to these changes, with two primary mechanisms\nbeing: (1) myofilament-dependent calcium release events, and (2) the activation\nof stretch-activated currents (SACs). In this computational investigation, we\nassessed the collective impact of these processes on mechanically-induced\nalternans that create an arrhythmogenic substrate during acute ischaemia. To\nappraise the potential involvement of MEC in ischaemia-induced arrhythmias, we\ndeveloped a coupled model of ventricular myocyte electrophysiology and\ncontraction including SACs and stretch-dependent calcium buffering and release.\nThe model, reflecting observed electrophysiological changes during ischaemia,\nwas exposed to a series of stretch protocols that replicated both physiological\nand pathological mechanical conditions. Pathologically realistic myofiber\nstretch variations revealed calcium sensitivity changes dependent on\nmyofilament, leading to alterations in cytosolic calcium concentrations. Under\ncalcium overload conditions, these changes resulted in electrical alternans.\nThe study implies that strain impacts cellular electrophysiology through\nmyofilament calcium release and SAC opening in ventricular mechano-electrical\nmodels, parameterised to available data. This supports experimental evidence\nsuggesting that both calcium-driven instability via MEC and SAC-induced effects\ncontribute to electrical alternans in acute ischaemia.", "category": "physics_bio-ph" }, { "text": "The Power of Many: A Physarum Swarm Steiner Tree Algorithm: We create a novel Physarum Steiner algorithm designed to solve the Euclidean\nSteiner tree problem. Physarum is a unicellular slime mold with the ability to\nform networks and fuse with other Physarum organisms. We use the simplicity and\nfusion of Physarum to create large swarms which independently operate to solve\nthe Steiner problem. The Physarum Steiner tree algorithm then utilizes a swarm\nof Physarum organisms which gradually find terminals and fuse with each other,\nsharing intelligence. The algorithm is also highly capable of solving the\nobstacle avoidance Steiner tree problem and is a strong alternative to the\ncurrent leading algorithm. The algorithm is of particular interest due to its\nnovel approach, rectilinear properties, and ability to run on varying shapes\nand topological surfaces.", "category": "physics_bio-ph" }, { "text": "Criteria for minimal model of driven polymer translocation: While the characteristics of the driven translocation for asymptotically long\npolymers are well understood, this is not the case for finite-sized polymers,\nwhich are relevant for real-world experiments and simulation studies. Most\nnotably, the behavior of the exponent $\\alpha$, which describes the scaling of\nthe translocation time with polymer length, when the driving force $f_p$ in the\npore is changed, is under debate. By Langevin dynamics simulations of regular\nand modified translocation models using the freely-jointed-chain polymer model\nwe find that a previously reported incomplete model, where the {\\it trans} side\nand fluctuations were excluded, gives rise to characteristics that are in stark\ncontradiction with those of the complete model, for which $\\alpha$ increases\nwith $f_p$. Our results suggest that contribution due to fluctuations is\nimportant. We construct a minimal model where dynamics is completely excluded\nto show that close alignment with a full translocation model can be achieved.\nOur findings set very stringent requirements for a minimal model that is\nsupposed to describe the driven polymer translocation correctly.", "category": "physics_bio-ph" }, { "text": "Load-dependent adaptation near zero load in the bacterial flagellar\n motor: The bacterial flagellar motor is an ion-powered transmembrane protein complex\nwhich drives swimming in many bacterial species. The motor consists of a\ncytoplasmic 'rotor' ring and a number of 'stator' units, which are bound to the\ncell wall of the bacterium. Recently, it has been shown that the number of\nfunctional torque-generating stator units in the motor depends on the external\nload, and suggested that mechanosensing in the flagellar motor is driven via a\n'catch bond' mechanism in the motor's stator units. We present a method that\nallows us to measure -- on a single motor -- stator unit dynamics across a\nlarge range of external loads, including near the zero-torque limit. By\nattaching superparamagnetic beads to the flagellar hook, we can control the\nmotor's speed via a rotating magnetic field. We manipulate the motor to four\ndifferent speed levels in two different ion-motive force (IMF) conditions. This\nframework allows for a deeper exploration into the mechanism behind\nload-dependent remodelling by separating out motor properties, such as rotation\nspeed and energy availability in the form of IMF, that affect the motor torque.", "category": "physics_bio-ph" }, { "text": "A twist in chiral interaction between biological helices: Using an exact solution for the pair interaction potential, we show that\nlong, rigid, chiral molecules with helical surface charge patterns have a\npreferential interaxial angle ~((RH)^1/2)/L, where L is the length of the\nmolecules, R is the closest distance between their axes, and H is the helical\npitch. Estimates based on this formula suggest a solution for the puzzle of\nsmall interaxial angles in a-helix bundles and in cholesteric phases of DNA.", "category": "physics_bio-ph" }, { "text": "Nanoplasmonic Tweezers Visualize Protein p53 Suppressing Unzipping of\n Single DNA-Hairpins: Here we report on the use of double-nanohole (DNH) optical tweezers as a\nlabel-free and free-solution single-molecule probe for protein-DNA\ninteractions. Using this approach, we demonstrate the unzipping of individual\n10 base pair DNA-hairpins, and quantify how tumor suppressor p53 protein delays\nthe unzipping. From the Arrhenius behavior, we find the energy barrier to\nunzipping introduced by p53 to be $2\\times 10^{-20}$ J, whereas cys135ser\nmutant p53 does not show suppression of unzipping, which gives clues to its\nfunctional inability to suppress tumor growth. This transformative approach to\nsingle molecule analysis allows for ultra-sensitive detection and\nquantification of protein-DNA interactions to revolutionize the fight against\ngenetic diseases.", "category": "physics_bio-ph" }, { "text": "Polymorphism and bistability in adherent cells: The optimal shapes attained by contractile cells on adhesive substrates are\ndetermined by the interplay between intracellular forces and adhesion with the\nextracellular matrix. We model the cell as a contractile film bounded by an\nelastic cortex and connected to the substrate via elastic links. When the\nadhesion sites are continuously distributed, optimal cell shape is constrained\nby the adhesion geometry, with a spread area sensitively dependent on the\nsubstrate stiffness and contractile tension. For discrete adhesion sites,\nequilibrium cell shape is convex at weak contractility, while developing local\nconcavities at intermediate values of contractility. Increasing contractility\nbeyond a critical value, controlled by mechanical and geometrical properties of\nadhesion, cell boundary undergoes a discontinuous transition to a star-shaped\nconfiguration with cusps and protrusions, accompanied by a region of\nbistability and hysteresis.", "category": "physics_bio-ph" }, { "text": "Pitfalls in the quantitative analysis of random walks and the mapping of\n single-molecule dynamics at the cellular scale: In recent years Bayesian Inference has become an efficient tool to analyse\nsingle molecule trajectories. Recently, high density single molecule tagging,\nLangevin Equation modelling and Bayesian Inference [10] have been used to infer\ndiffusion, force and potential fields at the full cell scale. In this short\ncomment, we point out pitfalls [1, 2] to avoid in single molecule analysis in\norder to get unbiased results and reliable fields at various scales.", "category": "physics_bio-ph" }, { "text": "Reduction of a kinetic model for Na+ channel activation, and fast and\n slow inactivation within a neural or cardiac membrane: A fifteen state kinetic model for Na+ channel gating that describes the\ncoupling between three activation sensors, a two-stage fast inactivation\nprocess and slow inactivated states, may be reduced to equations for a six\nstate system by application of the method of multiple scales. By expressing the\noccupation probabilities for closed states and the open state in terms of\nactivation and fast inactivation variables, and assuming that activation has a\nfaster relaxation than inactivation and that the activation sensors are\nmutually independent, the kinetic equations may be further reduced to rate\nequations for activation, and coupled fast and slow inactivation that describe\nspike frequency adaptation, a repetitive bursting oscillation in the neural\nmembrane, and a cardiac action potential with a plateau oscillation. The fast\ninactivation rate function is, in general, dependent on the activation variable\nm(t) but may be approximated by a voltage-dependent function, and the rate\nfunction for entry into the slow inactivated state is dependent on the fast\ninactivation variable.", "category": "physics_bio-ph" }, { "text": "Hindrances to precise recovery of cellular forces in fibrous biopolymer\n networks: How cells move through the three-dimensional extracellular matrix (ECM) is of\nincreasing interest in attempts to understand important biological processes\nsuch as cancer metastasis. Just as in motion on flat surfaces, it is expected\nthat experimental measurements of cell-generated forces will provide valuable\ninformation for uncovering the mechanisms of cell migration. However, the\nrecovery of forces in fibrous biopolymer networks may suffer from large errors.\nHere, within the framework of lattice-based models, we explore possible issues\nin force recovery by solving the inverse problem: how can one determine the\nforces cells exert to their surroundings from the deformation of the ECM? Our\nresults indicate that irregular cell traction patterns, the uncertainty of\nlocal fiber stiffness, the non-affine nature of ECM deformations and inadequate\nknowledge of network topology will all prevent the precise force determination.\nAt the end, we discuss possible ways of overcoming these difficulties.", "category": "physics_bio-ph" }, { "text": "Self-Motion Mechanism Of Chained Spherical Grains Cells: Cells are modeled with spherical grains connected each other. Each cell can\nshrink and swell by transporting its fluid content to other connected neighbor\nwhile still maintaining its density at constant value. As a spherical part of a\ncell swells it gains more pressure from its surrounding, while shrink state\ngains less pressure. Pressure difference between these two or more parts of\ncell will create motion force for the cell. For simplicity, cell is considered\nto have same density as its environment fluid and connections between parts of\ncell are virtually accommodated by a spring force. This model is also limited\nto 2-d case. Influence of parameters to cell motion will be presented. One\ngrain cell shows no motion, while two and more grains cell can perform a\nmotion.", "category": "physics_bio-ph" }, { "text": "A high performance membraneless microfluidic microbial fuel cell for\n stable, long-term benchtop operation under strong flow: Strong control over experimental conditions in microfluidic channels provides\na unique opportunity to study and optimize membraneless microbial fuel cells\n(MFCs), particularly with respect to the role of flow. However, improved\nperformance and transferability of results to the wider MFC community require\nimprovements to device stability under all applied operational conditions. To\naddress these challenges, we present an easy-to-fabricate membraneless MFC that\ncombines (i) O2 elimination via a gas diffusion barrier, (ii) integrated\ngraphite electrodes, and (iii) optimized electrode placement to avoid of\ncross-contamination under all applied flow rates. Attention to all of these\ndesign features in the same platform resulted in operation of a MFC with a\npure-culture anaerobic Geobacter sulfurreducens biofilm for half a year, six\ntimes longer than previously reported, without the use of an oxygen scavenger.\nAs a result of higher device stability under high flow rates, power densities\nwere four times higher than reported previously for microfluidic MFCs with the\nsame biofilm.", "category": "physics_bio-ph" }, { "text": "Complex nonlinear capacitance in outer hair cell macro-patches: effects\n of membrane tension: Outer hair cell (OHC) nonlinear capacitance (NLC) represents voltage sensor\ncharge movements of prestin (SLC26a5), the protein responsible for OHC\nelectromotility. Previous measures of NLC frequency response have employed\nmethods which did not assess the influence of dielectric loss (sensor charge\nmovements out of phase with voltage) that may occur, and such loss conceivably\nmay influence the frequency dependent activity of prestin. Here we evaluate\ncomplex capacitance of prestin out to 30 kHz and find that its frequency\nresponse determined using this approach coincides with all previous estimates.\nWe also show that membrane tension has no effect on the frequency response of\nprestin, despite substantial shifts in its voltage operating range, indicating\nthat prestin transition rate alterations do not account for the shifts. The\nmagnitude roll-off of prestin activity across frequency surpasses the\nreductions of NLC caused by salicylate treatments that are known to abolish\ncochlear amplification. Such roll-off must therefore limit the effectiveness if\nprestin in contributing to cochlear amplification at the very high acoustic\nfrequencies processed by some mammals.", "category": "physics_bio-ph" }, { "text": "The Dynamics and Infrared Spectrocopy of Monomeric and Dimeric Wild Type\n and Mutant Insulin: The infrared spectroscopy and dynamics of -CO labels in wild type and mutant\ninsulin monomer and dimer are characterized from molecular dynamics simulations\nusing validated force fields. It is found that the spectroscopy of monomeric\nand dimeric forms in the region of the amide-I vibration differs for residues\nB24-B26 and D24-D26, which are involved in dimerization of the hormone. Also,\nthe spectroscopic signatures change for mutations at position B24 from\nphenylalanine - which is conserved in many organisms and known to play a\ncentral role in insulin aggregation - to alanine or glycine. Using three\ndifferent methods to determine the frequency trajectories - solving the nuclear\nSchr\\\"odinger equation on an effective 1-dimensional potential energy curve,\ninstantaneous normal modes, and using parametrized frequency maps - lead to the\nsame overall conclusions. The spectroscopic response of monomeric WT and mutant\ninsulin differs from that of their respective dimers and the spectroscopy of\nthe two monomers in the dimer is also not identical. For the WT and F24A and\nF24G monomers spectroscopic shifts are found to be $\\sim 20$ cm$^{-1}$ for\nresidues (B24 to B26) located at the dimerization interface. Although the\ncrystal structure of the dimer is that of a symmetric homodimer, dynamically\nthe two monomers are not equivalent on the nanosecond time scale. Together with\nearlier work on the thermodynamic stability of the WT and the same mutants it\nis concluded that combining computational and experimental infrared\nspectroscopy provides a potentially powerful way to characterize the\naggregation state and dimerization energy of modified insulins.", "category": "physics_bio-ph" }, { "text": "Unique flow features of the silent southern Boobook owl wake during\n flapping flight: The mechanisms associated with an owls ability to fly silently have been the\nsubject of scientific interest for many decades and a source of inspiration in\nthe context of reducing noise in both flapping and non-flapping flight. Here,\nwe characterize the near wake dynamics and associated flow structures that are\nproduced by flying owls. The goal is to shed light on unique flow features that\nresult from the owls wing morphology and its motion during forward flapping\nflight. We study the wake of the southern boobook owl (Ninox boobook); a\nmid-sized owl, which shares the common feature of stealthy flight. Three\nindividual owls were flown, separately, in a climatic avian wind tunnel at\ntheir comfortable speed. The velocity field in the wake was sampled using\nlong-duration highspeed Particle Image Velocimetry (PIV) while the wings\nkinematics were imaged simultaneously using high speed video. The time series\nof velocity maps that were acquired over several consecutive wingbeat cycles\nenable us to characterize the wake patterns and associate them with the various\nphases of the wingbeat cycle. Results reveal that the owls wake is\nsignificantly different compared with other birds (western sandpiper, Calidris\nmauri; European starling, Strunus vulgaris). The near wake of the owl did not\nexhibit any apparent shedding of organized vortices. Instead, a more chaotic\nwake pattern is observed, in which the characteristic scales of vorticity\n(associated with turbulence) are substantially smaller in comparison to other\nbirds. Estimating the pressure field developed in the wake depicts that the owl\nreduces the pressure to approximately zero. It is therefore conjectured that\nowls manipulate the near wake to suppress the aeroacoustic signal by\ncontrolling the size of vortices generated in its wake, which are associated\nwith noise reduction through suppression of the pressure field", "category": "physics_bio-ph" }, { "text": "Geometry-sensitive protrusion growth directs confined cell migration: The migratory dynamics of cells can be influenced by the complex\nmicro-environment through which they move. It remains unclear how the motility\nmachinery of confined cells responds and adapts to their micro-environment.\nHere, we propose a biophysical mechanism for a geometry-dependent coupling\nbetween cellular protrusions and the nucleus that leads to directed migration.\nWe apply our model to geometry-guided cell migration to obtain insights into\nthe origin of directed migration on asymmetric adhesive micro-patterns and the\npolarization enhancement of cells observed under strong confinement.\nRemarkably, for cells that can choose between channels of different size, our\nmodel predicts an intricate dependence for cellular decision making as a\nfunction of the two channel widths, which we confirm experimentally.", "category": "physics_bio-ph" }, { "text": "Cardiac Alternans Arising from an Unfolded Border-Collision Bifurcation: Following an electrical stimulus, the transmembrane voltage of cardiac tissue\nrises rapidly and remains at a constant value before returning to the resting\nvalue, a phenomenon known as an action potential. When the pacing rate of a\nperiodic train of stimuli is increased above a critical value, the action\npotential undergoes a period-doubling bifurcation, where the resulting\nalternation of the action potential duration is known as alternans in the\nmedical literature. Existing cardiac models treat alternans either as a smooth\nor as a border-collision bifurcation. However, recent experiments in paced\ncardiac tissue reveal that the bifurcation to alternans exhibits hybrid\nsmooth/nonsmooth behaviors, which can be qualitatively described by a model of\nso-called unfolded border-collision bifurcation. In this paper, we obtain\nanalytical solutions of the unfolded border-collision model and use it to\nexplore the crossover between smooth and nonsmooth behaviors. Our analysis\nshows that the hybrid smooth/nonsmooth behavior is due to large variations in\nthe system's properties over a small interval of the bifurcation parameter,\nproviding guidance for the development of future models.", "category": "physics_bio-ph" }, { "text": "Validation and Comparison of Instrumented Mouthguards for Measuring Head\n Kinematics and Assessing Brain Deformation in Football Impacts: Because of the relatively rigid coupling between the upper dentition and the\nskull, instrumented mouthguards have been shown to be a viable way of measuring\nhead impact kinematics for assisting in understanding the underlying\nbiomechanics of concussions. This has led various companies and institutions to\nfurther develop instrumented mouthguards. However, their use as a research tool\nfor understanding concussive impacts makes quantification of their accuracy\ncritical, especially given the conflicting results from various recent studies.\nHere we present a study that uses a pneumatic impactor to deliver impacts\ncharacteristic to football to a Hybrid III headform, in order to validate and\ncompare five of the most commonly used instrumented mouthguards. We found that\nall tested mouthguards gave accurate measurements for the peak angular\nacceleration (mean relative error, MRE < 13%), the peak angular velocity (MRE <\n8%), brain injury criteria values (MRE < 13%) and brain deformation (described\nas maximum principal strain and fiber strain, calculated by a convolutional\nneural network based brain model, MRE < 9%). Finally, we found that the\naccuracy of the measurement varies with the impact locations yet is not\nsensitive to the impact velocity for the most part.", "category": "physics_bio-ph" }, { "text": "Effective spring constants for the elastically coupled insertions in\n membranes: In linear elastic theory, membrane deformation energy caused by inclusions\n(e.g., membrane-spanning peptides in lipid bilayers) can be rigorously\npresented in terms of coupled harmonic oscillators. The general expressions for\nthe corresponding \"effective spring constants\" are derived here for quite\ngeneral boundary conditions allowing, e.g., for the azimuthal variation of the\ncontact slope. The case of two insertions is considered in more details.", "category": "physics_bio-ph" }, { "text": "High Sensitivity and Specificity Biomechanical Imaging by Stimulated\n Brillouin Scattering Microscopy: Noncontact label-free biomechanical imaging is a crucial tool for unraveling\nthe mechanical properties of biological systems, which play critical roles in\nthe fields of engineering, physics, biology and medicine; yet, it represents a\nsignificant challenge in microscopy. Spontaneous Brillouin microscopy meets\nthis challenge, but often requires long acquisition times or lacks high\nspecificity for detecting biomechanical constituents with highly overlapping\nBrillouin bands. We developed stimulated Brillouin scattering (SBS) microscopy\nthat provides intrinsic noncontact biomechanical contrast and generates\nmechanical cross-sectional images inside large specimens, with high mechanical\nspecificity and pixel dwell times that are >10-fold improved over those of\nspontaneous Brillouin microscopy. We used SBS microscopy in different\nbiological applications, including the quantification of the high-frequency\ncomplex longitudinal modulus of the pharyngeal region of live wild-type\nCaenorhabditis elegans nematodes, imaging of the variations in the\nhigh-frequency viscoelastic response to osmotic stress in the head of living\nworms, and in vivo mechanical contrast mesoscopy of developing nematodes", "category": "physics_bio-ph" }, { "text": "Delineating corneal elastic anisotropy in a porcine model using\n non-contact optical coherence elastography and ex vivo mechanical tests: Objective: To compare non-contact acoustic micro-tapping optical coherence\nelastography (AuT-OCE) with destructive mechanical tests to confirm corneal\nelastic anisotropy.\n Design: Ex vivo, laboratory study with non-contact AuT-OCE followed by\nmechanical rheometry and extensometry.\n Subjects: Inflated cornea of whole-globe porcine eyes.\n Methods: A non-contact transducer was used to launch mechanical waves in the\ncornea that were imaged with phase-sensitive OCT at physiologically relevant\npressures. Reconstruction of both Young's modulus (E) and out-of-plane shear\nmodulus (G) in the cornea from experimental data was performed using a model of\na nearly incompressible transversally isotropic (NITI) medium. Samples were\nthen excised and parallel plate rheometry was performed to measure the shear\nmodulus G. Corneal samples were then subjected to strip extensomety to measure\nthe Young's modulus.\n Main Outcome Measures: Strong corneal anisotropy was confirmed with both\nAuT-OCE and mechanical tests, with the Young's and shear moduli differing by\nover an order of magnitude. These results show that AuT-OCE can quantify both\nmoduli with a non-contact, non-invasive, clinically translatable technique.", "category": "physics_bio-ph" }, { "text": "Theory on Plasmon Modes of the Cell Membranes: Considering the plasmon oscillation of each layer of the cell membranes as a\nquasi-particle, we introduce a simple model for the membrane collective charge\nexcitations, take into account the surface effective potential of the\nplasmon-plasmon interaction between two layers. By using the useful Bogoliubov\ntransformation method, we easily obtained the expressions of the frequencies of\nplasmon oscillations as a function of wave-number $k$ and membrane thickness\n$d$, magnitude of these frequencies is in the order of $\\sqrt{kd}$. Our results\nare in good agreement with ones obtained by E. Manousakis.", "category": "physics_bio-ph" }, { "text": "Disorder protects collagen networks from fracture: Collagen forms the structural scaffold of connective tissues in all mammals.\nTissues are remarkably resistant against mechanical deformations because\ncollagen molecules hierarchically self-assemble in fibrous networks that\nstiffen with increasing strain. Nevertheless, collagen networks do fracture\nwhen tissues are overloaded or subject to pathological conditions such as\naneurysms. Prior studies of the role of collagen in tissue fracture have mainly\nfocused on tendons, which contain highly aligned bundles of collagen. By\ncontrast, little is known about fracture of the orientationally more disordered\ncollagen networks present in many other tissues such as skin and cartilage.\nHere, we combine shear rheology of reconstituted collagen networks with\ncomputer simulations to investigate the primary determinants of fracture in\ndisordered collagen networks. We show that the fracture strain is controlled by\nthe coordination number of the network junctions, with less connected networks\nfracturing at larger strains. The hierarchical structure of collagen fine-tunes\nthe fracture strain by providing structural plasticity at the network and fiber\nlevel. Our findings imply that structural disorder provides a protective\nmechanism against network fracture that can optimize the strength of biological\ntissues.", "category": "physics_bio-ph" }, { "text": "Residue network in protein native structure belongs to the universality\n class of three dimensional critical percolation cluster: A single protein molecule is regarded as a contact network of amino-acid\nresidues. Some studies have indicated that this network is a small world\nnetwork (SWN), while other results have implied that this is a fractal network\n(FN). However, SWN and FN are essentially different in the dependence of the\nshortest path length on the number of nodes. In this paper, we investigate this\ndependence in the residue contact networks of proteins in native structures,\nand show that the networks are not SWN but FN. FN is generally characterized by\nseveral dimensions. Among them, we focus on three dimensions; the network\ntopological dimension $D_c$, the fractal dimension $D_f$, and the spectral\ndimension $D_s$. We find that proteins universally yield $D_c \\approx 1.9$,\n$D_f \\approx 2.5$ and $Ds \\approx 1.3$. These values are in surprisingly good\ncoincidence with those in three dimensional critical percolation cluster. Hence\nthe residue contact networks in the protein native structures belong to the\nuniversality class of three dimensional percolation cluster. The criticality is\nrelevant to the ambivalent nature of the protein native structures, i.e., the\ncoexistence of stability and instability, both of which are necessary for a\nprotein to function as a molecular machine or an allosteric enzyme.", "category": "physics_bio-ph" }, { "text": "Stability of gene regulatory networks: Homeostasis of protein concentrations in cells is crucial for their proper\nfunctioning, and this requires concentrations (at their steady-state levels) to\nbe stable to fluctuations. Since gene expression is regulated by proteins such\nas transcription factors (TFs), the full set of proteins within the cell\nconstitutes a large system of interacting components. Here, we explore factors\naffecting the stability of this system by coupling the dynamics of mRNAs and\nprotein concentrations in a growing cell. We find that it is possible for\nprotein concentrations to become unstable if the regulation strengths or system\nsize becomes too large, and that other global structural features of the\nnetworks can dramatically enhance the stability of the system. In particular,\ngiven the same number of proteins, TFs, number of interactions, and regulation\nstrengths, a network that resembles a bipartite graph with a lower fraction of\ninteractions that target TFs has a higher chance of being stable. By scrambling\nthe $\\textit{E. coli.}$ transcription network, we find that the randomized\nnetwork with the same number of regulatory interactions is much more likely to\nbe unstable than the real network. These findings suggest that constraints\nimposed by system stability could have played a role in shaping the existing\nregulatory network during the evolutionary process. We also find that contrary\nto what one might expect from random matrix theory and what has been argued in\nthe literature, the degradation rate of mRNA does not affect whether the system\nis stable.", "category": "physics_bio-ph" }, { "text": "Evidence for a Solenoid Phase of Supercoiled DNA: In mechanical manipulation experiments, a single DNA molecule overwound at\nconstant force undergoes a discontinuous drop in extension as it buckles and\nforms a superhelical loop (a plectoneme). Further overwinding the DNA, we\nobserve an unanticipated cascade of highly regular discontinuous extension\nchanges associated with stepwise plectoneme lengthening. This phenomenon is\nconsistent with a model in which the force-extended DNA forms barriers to\nplectoneme lengthening caused by topological writhe. Furthermore, accounting\nfor writhe in a fluctuating solenoid gives an improved description of the\nmeasured force-dependent effective torsional modulus of DNA, providing a\nreliable formula to estimate DNA torque. Our data and model thus provide\ncontext for further measurements and theories that capture the structures and\nmechanics of supercoiled biopolymers.", "category": "physics_bio-ph" }, { "text": "How the zebra got its stripes: Curvature-dependent diffusion orients\n Turing patterns on 3D surfaces: Many animals have patterned fur, feathers, or scales, such as the stripes of\na zebra. Turing models, or reaction-diffusion systems, are a class of\nmathematical models of interacting species that have been successfully used to\ngenerate animal-like patterns for many species. When diffusion of the inhibitor\nis high enough relative to the activator, a diffusion-driven instability can\nspontaneously form patterns. However, it is not just the type of pattern but\nalso the orientation that matters, and it remains unclear how this is done in\npractice. Here, we propose a mechanism by which the curvature of the surface\ninfluence the rate of diffusion, and can recapture the correct orientation of\nstripes on models of a zebra and of a cat in numerical simulations. Previous\nwork has shown how anisotropic diffusion can give stripe forming\nreaction-diffusion systems a bias in orientation. From the observation that\nzebra stripes run around the direction of highest curvature, that is around the\ntorso and legs, we apply this result by modifying the diffusion rate in a\ndirection based on the local curvature. These results show how local geometry\ncan influence the reaction dynamics to give robust, global-scale patterns.\nOverall, this model proposes a coupling between the system geometry and\nreaction-diffusion dynamics that can give global control over the patterning by\nusing only local curvature information. Such a model can give shape and\npositioning information in animal development without the need for spatially\ndependent morphogen gradients.", "category": "physics_bio-ph" }, { "text": "Low concentrated hydroxyectoine solutions in presence of DPPC lipid\n bilayers: a computer simulation study: The influence of hydroxyectoine on the properties of the aqueous solution in\npresence of DPPC lipid bilayers is studied via semi-isotropic constant pressure\n(NPT) Molecular Dynamics simulations. We investigate the solvent-co-solute\nbehavior in terms of Kirkwood-Buff integrals as well as hydrogen bond life\ntimes for an increasing hydroxyectoine concentration up to 0.148 mol/L. The\nobserved preferential exclusion mechanism identifies hydroxyectoine as a\nkosmotropic osmolyte. Our findings in regards to the DPPC lipid bilayer\nindicate an increase of the surface pressure as well as the solvent accessible\nsurface area in presence of higher hydroxyectoine concentrations. The results\nare in agreement to the outcome of recent experiments. With this study, we are\nable to validate the visibility of co-solute-solute-solvent effects for low and\nphysiologically relevant osmolyte concentrations.", "category": "physics_bio-ph" }, { "text": "Stress relaxation and creep experiments with the atomic force\n microscope: a unified method to calculate elastic moduli and viscosities of\n biomaterials (and cells): We show that the atomic force microscope can perform stress relaxation and\ncreep compliance measurements on living cells. We propose a method to obtain\nthe mechanical properties of the studied biomaterial: the relaxation time, the\nelastic moduli and the viscosity.", "category": "physics_bio-ph" }, { "text": "Virus Assembly Pathways inside a Host Cell: Simple RNA viruses self-assemble spontaneously and encapsulate their genome\ninto a shell called the capsid. This process is mainly driven by the attractive\nelectrostatic interaction between the positive charges on capsid proteins and\nthe negative charges on the genome. Despite its importance and many decades of\nintense research, how the virus selects and packages its native RNA inside the\ncrowded environment of a host cell cytoplasm in the presence of an abundance of\nnon-viral RNA and other anionic polymers, has remained a mystery. In this\npaper, we perform a series of simulations to monitor the growth of viral shells\nand find the mechanism by which cargo-coat protein interactions can impact the\nstructure and stability of the viral shells. We show that coat protein subunits\ncan assemble around a globular nucleic acid core by forming non-icosahedral\ncages, which have been recently observed in assembly experiments involving\nsmall pieces of RNA. We find that the resulting cages are strained and can\neasily be split into fragments along stress lines. This suggests that such\nmetastable non-icosahedral intermediates could be easily re-assembled into the\nstable native icosahedral shells if the larger wild-type genome becomes\navailable, despite the presence of myriad of non-viral RNAs.", "category": "physics_bio-ph" }, { "text": "Time-correlated forces and biological variability in cell motility: Cell motility is one of the most fundamental phenomena underlying biological\nprocesses that maintain living organisms alive. Here we introduce a simple\nmodel to describe the motility of cells which include not only time-correlated\ninternal forces but also the biological variability which is inherent of the\nintra-cellular biochemical processes. Such model allow us to derive exact\nexpressions for the mean-squared displacement and the effective time-dependent\ndiffusion coefficient which are compared to numerical results obtained from\nnon-markovian stochastic simulations. In addition, we show that the\nheterogeneity of persistence times lead to non-gaussian distributions which can\nbe obtained analytically and that were validated by the numerical simulations.\nOur results indicate that such model might be used to describe the behaviour\nobserved in experimental results obtained for isolated cells without external\nsignaling.", "category": "physics_bio-ph" }, { "text": "Self-consistent sharp interface theory of active condensate dynamics: Biomolecular condensates help organize the cell cytoplasm and nucleoplasm\ninto spatial compartments with different chemical compositions. A key feature\nof such compositional patterning is the local enrichment of enzymatically\nactive biomolecules which, after transient binding via molecular interactions,\ncatalyze reactions among their substrates. Thereby, biomolecular condensates\nprovide a spatial template for non-uniform concentration profiles of\nsubstrates. In turn, the concentration profiles of substrates, and their\nmolecular interactions with enzymes, drive enzyme fluxes which can enable novel\nnon-equilibrium dynamics. To analyze this generic class of systems, with a\ncurrent focus on self-propelled droplet motion, we here develop a\nself-consistent sharp interface theory. In our theory, we diverge from the\nusual bottom-up approach, which involves calculating the dynamics of\nconcentration profiles based on a given chemical potential gradient. Instead,\nreminiscent of control theory, we take the reverse approach by deriving the\nchemical potential profile and enzyme fluxes required to maintain a desired\ncondensate form and dynamics. The chemical potential profile and currents of\nenzymes come with a corresponding power dissipation rate, which allows us to\nderive a thermodynamic consistency criterion for the passive part of the system\n(here, reciprocal enzyme-enzyme interactions). As a first use case of our\ntheory, we study the role of reciprocal interactions, where the transport of\nsubstrates due to reactions and diffusion is, in part, compensated by\nredistribution due to molecular interactions. More generally, our theory\napplies to mass-conserved active matter systems with moving phase boundaries.", "category": "physics_bio-ph" }, { "text": "Label-free optical quantification of material composition of suspended\n virus-gold nanoparticle complexes: The interaction between metallic and biological nanoparticles (NPs) is widely\nused in various biotechnology and biomedical applications. However, detailed\ncharacterization of this type of interaction is challenging due to a lack of\nhigh-throughput techniques that can quantify both size and composition of\nsuspended NP complexes. Here, we introduce a technique called ``twilight\nnanoparticle tracking analysis'' (tNTA) and demonstrate that it provides a\nquantitative relationship between the measured optical signal and the\ncomposition of suspended dielectric-metal NP complexes. We assess the\nperformance of tNTA by analyzing the selective binding of tannic acid-modified\ngold nanoparticles (TaAuNPs) to herpes simplex viruses (HSV). Our results show\nthat TaAuNPs bind specifically to HSV without causing substantial changes in\nthe size or refractive index of the virus, suggesting that the binding does not\ncause virus disruption. Instead, the anti-viral properties of TaAuNPs appear to\nstem from direct particle binding to the virus.", "category": "physics_bio-ph" }, { "text": "Equilibrium insertion of nanoscale objects into phospholipid bilayers: Certain membrane proteins, peptides, nanoparticles and nanotubes have rigid\nstructure and fixed shape. They are often viewed as spheres and cylinders with\ncertain surface properties. Single Chain Mean Field theory is used to model the\nequilibrium insertion of nanoscale spheres and rods into the phospholipid\nbilayer. The equilibrium structures and the resulting free energies of the\nnano-objects in the bilayer allow to distinguish different orientations in the\nbilayer and estimate the energy barrier of insertion.", "category": "physics_bio-ph" }, { "text": "Twist neutrality, a zero sum rule for oriented closed space curves with\n applications to circular DNA: The interplay between global constraints and local material properties of\nchain molecules is a subject of emerging interest. Studies of molecules that\nare intrinsically chiral, such as double-stranded DNA, is one example. Their\nproperties generally depend on the local geometry, i.e. on curvature and\ntorsion, yet the paths of closed molecules are globally restricted by topology.\nMolecules that fulfill a twist neutrality condition, a zero sum rule for the\nincremental change in the rate of winding along the curve, will behave\nneutrally to strain. This has implications for plasmids. For small circular\nmicroDNAs it follows that there must exist a minimum length for these to be\ndouble-stranded. It also follows that all microDNAs longer than the minimum\nlength must be concave. This counterintuitive result is consistent with the\nkink-like appearance which has been observed for circular DNA. A prediction for\nthe total negative curvature of a circular microDNA is given as a function of\nits length.", "category": "physics_bio-ph" }, { "text": "Reverse-time analysis and boundary classification of directional\n biological dynamics with multiplicative noise: The dynamics of living systems often serves the purpose of reaching\nfunctionally important target states. We previously proposed a theory to\nanalyze stochastic biological dynamics evolving towards target states in\nreverse time. However, a large class of systems in biology can only be\nadequately described using state-dependent noise, which had not been discussed.\nFor example, in gene regulatory networks, biochemical signaling networks or\nneuronal circuits, count fluctuations are the dominant noise component. We\ncharacterize such dynamics as an ensemble of target state aligned (TSA)\ntrajectories and characterize its temporal evolution in reverse-time by\ngeneralized Fokker-Planck and stochastic differential equations with\nmultiplicative noise. We establish the classification of boundary conditions\nfor target state modeling for a wide range of power law dynamics, and derive a\nuniversal low-noise approximation of the final phase of target state\nconvergence. Our work expands the range of theoretically tractable systems in\nbiology and enables novel experimental design strategies for systems that\ninvolve target states.", "category": "physics_bio-ph" }, { "text": "Free energy barrier for melittin reorientation from a membrane-bound\n state to a transmembrane state: An important step in a phospholipid membrane pore formation by melittin\nantimicrobial peptide is a reorientation of the peptide from a surface into a\ntransmembrane conformation. In this work we perform umbrella sampling\nsimulations to calculate the potential of mean force (PMF) for the\nreorientation of melittin from a surface-bound state to a transmembrane state\nand provide a molecular level insight into understanding peptide and lipid\nproperties that influence the existence of the free energy barrier. The PMFs\nwere calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We\nobserve that the free energy barrier is reduced when the P/L ratio increased.\nIn addition, we study the cooperative effect; specifically we investigate if\nthe barrier is smaller for a second melittin reorientation, given that another\nneighboring melittin was already in the transmembrane state. We observe that\nindeed the barrier of the PMF curve is reduced in this case, thus confirming\nthe presence of a cooperative effect.", "category": "physics_bio-ph" }, { "text": "The Role of Protein Fluctuation Correlations in Electron Transfer in\n Photosynthetic Complexes: We consider the dependence of the electron transfer in photosynthetic\ncomplexes on correlation properties of random fluctuations of the protein\nenvironment. The electron subsystem is modeled by a finite network of connected\nelectron (exciton) sites. The fluctuations of the protein environment are\nmodeled by random telegraph processes, which act either collectively\n(correlated) or independently (uncorrelated) on the electron sites. We derived\nan exact closed system of first-order linear differential equations with\nconstant coefficients, for the average density matrix elements and for their\nfirst moments. Under some conditions, we obtain analytic expressions for the\nelectron transfer rates. We compare the correlated and uncorrelated regimes,\nand demonstrated numerically that the uncorrelated fluctuations of the protein\nenvironment can, under some conditions, either increase or decrease the\nelectron transfer rates.", "category": "physics_bio-ph" }, { "text": "A time series model of CDS sequences in complete genome: A time series model of CDS sequences in complete genome is proposed.\n A map of DNA sequence to integer sequence is given. The correlation\ndimensions and Hurst exponents of CDS sequences in complete genome of bacteria\nare calculated. Using the average of correlation dimensions, some interesting\nresults are obtained.", "category": "physics_bio-ph" }, { "text": "MoCL: Data-driven Molecular Fingerprint via Knowledge-aware Contrastive\n Learning from Molecular Graph: Recent years have seen a rapid growth of utilizing graph neural networks\n(GNNs) in the biomedical domain for tackling drug-related problems. However,\nlike any other deep architectures, GNNs are data hungry. While requiring labels\nin real world is often expensive, pretraining GNNs in an unsupervised manner\nhas been actively explored. Among them, graph contrastive learning, by\nmaximizing the mutual information between paired graph augmentations, has been\nshown to be effective on various downstream tasks. However, the current graph\ncontrastive learning framework has two limitations. First, the augmentations\nare designed for general graphs and thus may not be suitable or powerful enough\nfor certain domains. Second, the contrastive scheme only learns representations\nthat are invariant to local perturbations and thus does not consider the global\nstructure of the dataset, which may also be useful for downstream tasks.\nTherefore, in this paper, we study graph contrastive learning in the context of\nbiomedical domain, where molecular graphs are present. We propose a novel\nframework called MoCL, which utilizes domain knowledge at both local- and\nglobal-level to assist representation learning. The local-level domain\nknowledge guides the augmentation process such that variation is introduced\nwithout changing graph semantics. The global-level knowledge encodes the\nsimilarity information between graphs in the entire dataset and helps to learn\nrepresentations with richer semantics. The entire model is learned through a\ndouble contrast objective. We evaluate MoCL on various molecular datasets under\nboth linear and semi-supervised settings and results show that MoCL achieves\nstate-of-the-art performance.", "category": "physics_bio-ph" }, { "text": "SMILE Microscopy : fast and single-plane based super-resolution volume\n imaging: Fast 3D super-resolution imaging is essential for decoding rapidly occurring\nbiological processes. Encoding single molecules to their respective planes\nenable simultaneous multi-plane super-resolution volume imaging. This saves the\ndata-acquisition time and as a consequence reduce radiation-dose that lead to\nphotobleaching and other undesirable photochemical reactions. Detection and\nsubsequent identification of the locus of individual molecule (both on the\nfocal plane and off-focal planes) holds the key. Experimentally, this is\nachieved by accurate calibration of system PSF size and its natural spread in\noff-focal planes using sub-diffraction fluorescent beads. Subsequently the\nidentification and sorting of single molecules that belong to different axial\nplanes is carried out (by setting multiple cut-offs to respective PSFs).\nSimultaneous Multiplane Imaging based Localization Encoded (SMILE) microscopy\ntechnique eliminates the need for multiple z-plane scanning and thereby\nprovides a truly simultaneous multiplane super-resolution imaging.", "category": "physics_bio-ph" }, { "text": "Mechanical Acceleration of Capture and Detection Rate of DNA Molecules\n by Motorizing Bio-Opto-Plasmonic Microsensors: Efficient capture and detection of minute amount of deoxyribonucleic acid\n(DNA) molecules are pivotal for an array of modern gene technologies which are\nwidely utilized in medical, forensic and defense applications, including DNA\nextraction, preconcentration, and separation. In this work, we propose a\nrational mechanism to substantially accelerate the capture and detection\nefficiency of DNA molecules by actively motorizing designed Raman microsensors.\nAt least 4-fold enhancement has been achieved on the microsensors rotating at\n1200 rpm. The process is monitored dynamically and in-situ from the biosilica\nbased microsensors, owing to the ultrasensitivity provided by the\nopto-plasmonic enhancement. The fundamental working mechanism is investigated\nsystematically, and can be attributed to the Nernst diffusion layer thinning\neffect induced by mechanical motions. This research initiated a new and\nreliable approach for remarkably enhancing the capture and detection efficiency\nof biomolecules, which could make far-reaching impact to biosensing, DNA\ntechnologies, and microfluidic Total Analysis Systems.", "category": "physics_bio-ph" }, { "text": "The one-message-per-cell-cycle rule: A conserved minimum transcription\n level for essential genes: The inherent stochasticity of cellular processes leads to significant\ncell-to-cell variation in protein abundance. Although this noise has already\nbeen characterized and modeled, its broader implications and significance\nremain unclear. In this paper, we revisit the noise model and identify the\nnumber of messages transcribed per cell cycle as the critical determinant of\nnoise. In yeast, we demonstrate that this quantity predicts the non-canonical\nscaling of noise with protein abundance, as well as quantitatively predicting\nits magnitude. We then hypothesize that growth robustness requires an upper\nceiling on noise for the expression of essential genes, corresponding to a\nlower floor on the transcription level. We show that just such a floor exists:\na minimum transcription level of one message per cell cycle is conserved\nbetween three model organisms: Escherichia coli, yeast, and human. Furthermore,\nall three organisms transcribe the same number of messages per gene, per cell\ncycle. This common transcriptional program reveals that robustness to noise\nplays a central role in determining the expression level of a large fraction of\nessential genes, and that this fundamental optimal strategy is conserved from\nE. coli to human cells.", "category": "physics_bio-ph" }, { "text": "Continuum percolation theory of epimorphic regeneration: A biophysical model of epimorphic regeneration based on a continuum\npercolation process of fully penetrable disks in two dimensions is proposed.\nAll cells within a randomly chosen disk of the regenerating organism are\nassumed to receive a signal in the form of a circular wave as a result of the\naction/reconfiguration of neoblasts and neoblast-derived mesenchymal cells in\nthe blastema. These signals trigger the growth of the organism, whose cells\nread, on a faster time scale, the electric polarization state responsible for\ntheir differentiation and the resulting morphology. In the long time limit, the\nprocess leads to a morphological attractor that depends on experimentally\naccessible control parameters governing the blockage of cellular gap junctions\nand, therefore, the connectivity of the multicellular ensemble. When this\nconnectivity is weakened, positional information is degraded leading to more\nsymmetrical structures. This general theory is applied to the specifics of\nplanaria regeneration. Computations and asymptotic analyses made with the model\nshow that it correctly describes a significant subset of the most prominent\nexperimental observations, notably anterior-posterior polarization (and its\nloss) or the formation of four-headed planaria.", "category": "physics_bio-ph" }, { "text": "Force spectroscopy with electromagnetic tweezers: Force spectroscopy using magnetic tweezers (MT) is a powerful method to probe\nthe physical characteristics of single polymers. Typically, molecules are\nfunctionalized for specific attachment to a glass surface at one end and a\nmicron-scale paramagnetic beads at the other. By applying an external magnetic\nfield, multiple molecules can be stretched and twisted simultaneously without\nexposure to potentially damaging radiation. The majority of MT utilize moving\npermanent magnets to produce the forces on the beads (and the molecule under\ntest). However, translating and rotating the permanent magnets may require\nexpensive precision actuators, limits the rate at which force is changed, and\nmay induce vibrations that disturb tether dynamics. Alternatively, the magnetic\nfield can be produced through an electromagnet which allows much faster force\nmodulation and eliminates motor-associated vibration. Here, we describe a\nlow-cost quadrapolar electromagnetic tweezer design capable of manipulating\nDNA-tethered MyOne paramagnetic beads with forces of up to 20 pN. The\nsolid-state nature of the generated B-field modulated along two axes is\nconvenient for accessing the range of forces and torques relevant for studying\nthe activity of DNA motor enzymes like polymerases and helicases. Our design\nspecifically leverages technology available at an increasing number university\nmaker spaces and student-run machine shops. Thus, our design is not only\napplicable to a wide range biophysical research questions, but also an\naccessible tool for undergraduate education.", "category": "physics_bio-ph" }, { "text": "Structural Effects of Small Molecules on Phospholipid Bilayers\n Investigated by Molecular Simulations: We summarize and compare recent Molecular Dynamics simulations on the\ninteractions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid\ncrystalline phase with a number of small molecules including trehalose, a\ndisaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar\nmolecules tend to stabilize the structure of the bilayer as they bridge\nadjacent lipid headgroups. They do not strongly change the structure of the\nbilayer. Alcohols and DMSO destabilize the bilayer as they increase its area\nper molecule in the bilayer plane and decrease the order parameter. Alcohols\nhave a stronger detrimental effect than DMSO. The observables which we compare\nare the area per molecule in the plane of the bilayer, the membrane thickness,\nand the NMR order parameter of DPPC hydrocarbon tails. The area per molecule\nand the order parameter are very well correlated whereas the bilayer thickness\nis not necessarily correlated with them.", "category": "physics_bio-ph" }, { "text": "The younger flagellum coordinates the beating in C. reinhardtii: Eukaryotes swim with coordinated flagellar (ciliary) beating and steer by\nfine-tuning the coordination. The model organism for studying flagellate\nmotility, C. reinhardtii (CR), employs synchronous, breast-stroke-like\nflagellar beating to swim, and it modulates the beating amplitudes\ndifferentially to steer. This strategy hinges on both inherent flagellar\nasymmetries (e.g. different response to chemical messengers) and such\nasymmetries being effectively coordinated in the synchronous beating. In CR,\nthe synchrony of beating is known to be supported by a mechanical connection\nbetween flagella, however, how flagellar asymmetries persist in the synchrony\nremains elusive. For example, it has been speculated for decades that one\nflagellum leads the beating, as its dynamic properties (i.e. frequency,\nwaveform, etc.) appear to be copied by the other one. In this study, we combine\nexperiments, computations, and modeling efforts to elucidate the roles played\nby each flagellum in synchronous beating. With a non-invasive technique to\nselectively load each flagellum, we show that the coordinated beating\nessentially responds to only load exerted on the cis flagellum; and that such\nasymmetry in response derives from a unilateral coupling between the two\nflagella. Our results highlight a distinct role for each flagellum in\ncoordination and have implication for biflagellates tactic behaviors.", "category": "physics_bio-ph" }, { "text": "Statistical analysis of motion contrast in optical coherence tomography\n angiography: Optical coherence tomography angiography (Angio-OCT), mainly based on the\ntemporal dynamics of OCT scattering signals, has found a range of potential\napplications in clinical and scientific research. Based on the model of random\nphasor sums, temporal statistics of the complex-valued OCT signals are\nmathematically described. Statistical distributions of the amplitude\ndifferential and complex differential Angio-OCT signals are derived. The\ntheories are validated through the flow phantom and live animal experiments.\nUsing the model developed, the origin of the motion contrast in Angio-OCT is\nmathematically explained, and the implications in the improvement of motion\ncontrast are further discussed, including threshold determination and its\nresidual classification error, averaging method, and scanning protocol. The\nproposed mathematical model of Angio-OCT signals can aid in the optimal design\nof the system and associated algorithms.", "category": "physics_bio-ph" }, { "text": "Mechanically-driven spreading of bacterial populations: The effect of mechanical interactions between cells in the spreading of\nbacterial populations was investigated in one-dimensional space. A\ncontinuum-mechanics approach, comprising cell migration, proliferation, and\nexclusion processes, was employed to elucidate the dynamics. The consequent\nnonlinear reaction-diffusion-like equation describes the constitution dynamics\nof a bacterial population. In this model, bacterial cells were treated as\nrod-like particles that interact with each other through hard-core repulsion,\nwhich introduces the exclusion effect that causes bacterial populations to\nmigrate quickly and at high density. The propagation of bacterial density as a\ntraveling wave front over extended times was also analysed. The analytical and\nnumerical solutions revealed that the front speed was enhanced by the exclusion\nprocess, which depended upon the cell-packing fraction. Finally, we\nqualitatively compared our theoretical results with experimental evidence.", "category": "physics_bio-ph" }, { "text": "Termite mounds harness diurnal temperature oscillations for ventilation: Many species of millimetric fungus-harvesting termites collectively build\nuninhabited, massive mound structures enclosing a network of broad tunnels\nwhich protrude from the ground meters above their subterranean nests. It is\nwidely accepted that the purpose of these mounds is to give the colony a\ncontrolled micro-climate in which to raise fungus and brood by managing heat,\nhumidity, and respiratory gas exchange. While different hypotheses such as\nsteady and fluctuating external wind and internal metabolic heating have been\nproposed for ventilating the mound, the absence of direct in-situ measurement\nof internal air flows has precluded a definitive mechanism for this critical\nphysiological function. By measuring diurnal variations in flow through the\nsurface conduits of the mounds of the species Odontotermes obesus, we show that\na simple combination of geometry, heterogeneous thermal mass and porosity\nallows the mounds to use diurnal ambient temperature oscillations for\nventilation. In particular, the thin outer flute-like conduits heat up rapidly\nduring the day relative to the deeper chimneys, pushing air up the flutes and\ndown the chimney in a closed convection cell, with the converse situation at\nnight. These cyclic flows in the mound flush out $\\text{CO}_2$ from the nest\nand ventilate the colony, in a novel example of deriving useful work from\nthermal oscillations.", "category": "physics_bio-ph" }, { "text": "Nanoparticle diffusion in sheared cellular blood flow: Using a multiscale blood flow solver, the complete diffusion tensor of\nnanoparticle (NP) in sheared cellular blood flow is calculated over a wide\nrange of shear rate and haematocrit. In the short-time regime, NPs exhibit\nanomalous dispersive behaviors under high shear and high haematocrit due to the\ntransient elongation and alignment of the red blood cells (RBCs). In the\nlong-time regime, the NP diffusion tensor features high anisotropy.\nParticularly, there exists a critical shear rate ($\\sim$100 $s^{-1}$) around\nwhich the shear-rate dependence of the diffusivity tensor changes from linear\nto nonlinear scale. Above the critical shear rate, the cross-stream diffusivity\nterms vary sublinearly with shear rate, while the longitudinal term varies\nsuperlinearly. The dependence on haematocrit is linear in general except at\nhigh shear rates, where a sublinear scale is found for the vorticity term and a\nquadratic scale for the longitudinal term. Through analysis of the suspension\nmicrostructure and numerical experiments, the nonlinear hemorheological\ndependence of the NP diffusion tensor is attributed to the streamwise\nelongation and cross-stream contraction of RBCs under high shear, quantified by\na Capillary number. The RBC size is shown to be the characteristic length scale\naffecting the RBC-enhanced shear-induced diffusion (RESID), while the NP size\nat submicron exhibits negligible influence on the RESID. Based on the observed\nscaling behaviors, empirical correlations are proposed to bridge the NP\ndiffusion tensor to specific shear rate and haematocrit. The characterized NP\ndiffusion tensor provides a constitutive relation that can lead to more\neffective continuum models to tackle large-scale NP biotransport applications.", "category": "physics_bio-ph" }, { "text": "Collective dynamics of self-propelled particles with variable speed: Understanding the organization of collective motion in biological systems is\nan ongoing challenge. In this Paper we consider a minimal model of\nself-propelled particles with variable speed. Inspired by experimental data\nfrom schooling fish, we introduce a power-law dependency of the speed of each\nparticle on the degree of polarization order in its neighborhood. We derive\nanalytically a coarse-grained continuous approximation for this model and find\nthat, while the variable speed rule does not change the details of the ordering\ntransition leading to collective motion, it induces an inverse power-law\ncorrelation between the speed or the local polarization order and the local\ndensity. Using numerical simulations, we verify the range of validity of this\ncontinuous description and explore regimes beyond it. We discover, in\ndisordered states close to the transition, a phase-segregated regime where most\nparticles cluster into almost static groups surrounded by isolated high-speed\nparticles. We argue that the mechanism responsible for this regime could be\npresent in a wide range of collective motion dynamics.", "category": "physics_bio-ph" }, { "text": "A low-Reynolds-number treadmilling swimmer near a semi-infinite wall: We investigate the behavior of a treadmilling microswimmer in a\ntwo-dimensional unbounded domain with a semi-infinite no-slip wall. The wall\ncan also be regarded as a probe or pipette inserted into the flow. We solve the\ngoverning evolution equations in an analytical form and numerically calculate\ntrajectories of the swimmer for several different initial positions and\norientations. We then compute the probability that the treadmilling organism\ncan escape the vicinity of the wall. We find that many trajectories in a\n'wedge' around the wall are likely to escape. This suggests that inserting a\nprobe or pipette in a suspension of organism may push away treadmilling\nswimmers.", "category": "physics_bio-ph" }, { "text": "Phoresis and Enhanced Diffusion Compete in Enzyme Chemotaxis: Chemotaxis of enzymes in response to gradients in the concentration of their\nsubstrate has been widely reported in recent experiments, but a basic\nunderstanding of the process is still lacking. Here, we develop a microscopic\ntheory for chemotaxis, valid for enzymes and other small molecules. Our theory\nincludes both non-specific interactions between enzyme and substrate, as well\nas complex formation through specific binding between the enzyme and the\nsubstrate. We find that two distinct mechanisms contribute to enzyme\nchemotaxis: a diffusiophoretic mechanism due to the non-specific interactions,\nand a new type of mechanism due to binding-induced changes in the diffusion\ncoefficient of the enzyme. The latter chemotactic mechanism points towards\nlower substrate concentration if the substrate enhances enzyme diffusion, and\ntowards higher substrate concentration if the substrate inhibits enzyme\ndiffusion. For a typical enzyme, attractive phoresis and binding-induced\nenhanced diffusion will compete against each other. We find that phoresis\ndominates above a critical substrate concentration, whereas binding-induced\nenhanced diffusion dominates for low substrate concentration. Our results\nresolve an apparent contradiction regarding the direction of urease chemotaxis\nobserved in experiments, and in general clarify the relation between enhanced\ndiffusion and chemotaxis of enzymes. Finally, we show that the competition\nbetween the two distinct chemotactic mechanisms may be used to engineer\nnanomachines that move towards or away from regions with a specific substrate\nconcentration.", "category": "physics_bio-ph" }, { "text": "Steps in the bacterial flagellar motor: The bacterial flagellar motor is a highly efficient rotary machine used by\nmany bacteria to propel themselves. It has recently been shown that at low\nspeeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437,\n916--919]. Here we propose a simple physical model that accounts for this\nstepping behavior as a random walk in a tilted corrugated potential that\ncombines torque and contact forces. We argue that the absolute angular position\nof the rotor is crucial for understanding step properties, and show this\nhypothesis to be consistent with the available data, in particular the\nobservation that backward steps are smaller on average than forward steps. Our\nmodel also predicts a sublinear torque-speed relationship at low torque, and a\npeak in rotor diffusion as a function of torque.", "category": "physics_bio-ph" }, { "text": "A minimal reaction-diffusion neural model generates $\\textit{C.\n elegans}$ undulation: The small (1 mm) nematode $\\textit{Caenorhabditis elegans}$ (Corsi [1],\nwormbook.org) has become widely used as a model organism; in particular, the\n$\\textit{C. elegans}$ connectome has been completely mapped, and $\\textit{C.\nelegans}$ locomotion has been widely studied. We describe a minimal\nreaction-diffusion model for the locomotion of $\\textit{C. elegans}$, using as\na framework a simplified, stylized \"descending pathway\" of neurons as central\npattern generator (CPG) (Xu et al., Proceedings of the National Academy of\nSciences 115, 2018). Finally, we realize a model of the required oscillations\nand coupling with a network of coupled Keener (IEEE Transactions on Systems,\nMan, and Cybernetics SMC-13, 1983 [3]) analog neurons. Note that Olivares et\nal. (BioRxiv 710566, 2020 [4]) present a likely more realistic model more\ndistributed CPG. We use the simpler simulation to show that a small network of\nFitzHugh-Nagumo neurons (one of the simplest neuronal models) can generate key\nfeatures of $\\textit{C. elegans}$ undulation, and thus locomotion, yielding a\nminimal, biomimetic model as a building block for further exploring $\\textit{C.\nelegans}$ locomotion.", "category": "physics_bio-ph" }, { "text": "Theory of morphological transformation of viral capsid shells during\n maturation process: In the frame of the Landau-Ginzburg formalism we propose a minimal\nphenomenological model for a morphological transformation in viral capsid\nshells. The transformation takes place during virus maturation process which\nrenders virus infectious. The theory is illustrated on the example of the HK97\nbacteriophage and viruses with similar morphological changes in the protective\nprotein shell. The transformation is shown to be a structural phase transition\ndriven by two order parameters. The first order parameter describes the\nisotropic expansion of the protein shell while the second one is responsible\nfor the shape symmetry breaking and the resulting shell faceting. The group\ntheory analysis and the resulting thermodynamic model make it possible to\nchoose the parameter which discriminates between the icosahedral shell faceting\noften observed in viral capsids and the dodecahedral one observed in viruses of\nthe Parvovirus family. Calculated phase diagram illustrates the discontinuous\ncharacter of the virus morphological transformation and shows two qualitatively\ndifferent paths of the transformation in a function of two main external\nthermodynamic parameters of the in vitro and in vivo experiments.", "category": "physics_bio-ph" }, { "text": "Coordinated appendages accumulate more energy to self-right on the\n ground: Animals and robots must right themselves after flipping over on the ground.\nThe discoid cockroach pushes its wings against the ground in an attempt to\ndynamically self-right by a somersault. However, because this maneuver is\nstrenuous, the animal often fails to overcome the potential energy barrier and\nmakes continual attempts. In this process, the animal flails its legs, whose\nlateral perturbation eventually leads it to roll to the side to self-right. Our\nprevious work developed a cockroach-inspired robot capable of leg-assisted,\nwinged self-righting, and a robot simulation study revealed that the outcome of\nthis strategy depends sensitively on wing-leg coordination (measured by the\nphase between their motions). Here, we further elucidate why this is the case\nby developing a template to model the complex hybrid dynamics resulting from\ndiscontinuous contact and actuation. We used the template to calculate the\npotential energy barrier that the body must overcome to self-right, mechanical\nenergy contribution by wing pushing and leg flailing, and mechanical energy\ndissipation due to wing-ground collision. The template revealed that wing-leg\ncoordination (phase) strongly affects self-righting outcome by changing\nmechanical energy budget. Well-coordinated appendage motions (good phase)\naccumulate more mechanical energy than poorly-coordinated motions (bad phase),\nthereby better overcoming the potential energy barrier to self-right more\nsuccessfully. Finally, we demonstrated practical use of the template for\npredicting a new control strategy to further increase self-righting performance\nand informing robot design.", "category": "physics_bio-ph" }, { "text": "Current reversal and exclusion processes with history-dependent random\n walks: A class of exclusion processes in which particles perform history-dependent\nrandom walks is introduced, stimulated by dynamic phenomena in some biological\nand artificial systems. The particles locally interact with the underlying\nsubstrate by breaking and reforming lattice bonds. We determine the\nsteady-state current on a ring, and find current-reversal as a function of\nparticle density. This phenomenon is attributed to the non-local interaction\nbetween the walkers through their trails, which originates from strong\ncorrelations between the dynamics of the particles and the lattice. We\nrationalize our findings within an effective description in terms of\nquasi-particles which we call front barriers. Our analytical results are\ncomplemented by stochastic simulations.", "category": "physics_bio-ph" }, { "text": "Reaction-diffusion model for STIM-ORAI interaction: the role of ROS and\n mutations: Release of $Ca^{2+}$ from endoplasmatic retriculum (ER) $Ca^{2+}$ stores\ncauses stromal interaction molecules (STIM) in the ER membrane and ORAI\nproteins in the plasma membrane (PM) to interact and form the $Ca^{2+}$ release\nactivated $Ca^{2+}$ (CRAC) channels, which represent a major $Ca^{2+}$ entry\nroute in non-excitable cells and thus control various cell functions. It is\nexperimentally possible to mutate ORAI1 proteins and therefore modify,\nespecially block, the $Ca^{2+}$ influx into the cell. On the basis of the model\nof Hoover and Lewis (2011) [Hoover P J and Lewis R S, 2011], we formulate a\nreaction-diffusion model to quantify the STIM1-ORAI1 interaction during CRAC\nchannel formation and analyze different ORAI1 channel stoichiometries and\ndifferent ratios of STIM1 and ORAI1 in comparison with experimental data. We\nincorporate the inhibition of ORAI1 channels by ROS into our model and\ncalculate its contribution to the CRAC channel amplitude. We observe a large\ndecrease of the CRAC channel amplitude evoked by mutations of ORAI1 proteins.", "category": "physics_bio-ph" }, { "text": "An Accurate Numerical Solution to the Kinetics of Breakable Filament\n Assembly: Proteinaceous aggregation occurs through self-assembly-- a process not\nentirely understood. In a recent article [1], an analytical theory for amyloid\nfibril growth via secondary rather than primary nucleation was presented.\nRemarkably, with only a single kinetic parameter, the authors were able to\nunify growth characteristics for a variety of experimental data. In essence,\nthey seem to have uncovered the underlying allometric laws governing the\nevolution of filament elongation simply from two coupled non-linear ordinary\ndifferential equations (ODEs) stemming from a master equation. While this work\nadds significantly to our understanding of filament self-assembly, it required\nan approximate analytical solution representation. Here, we show that the same\nresults are found by purely numerical means once a straightforward and reliable\nnumerical solution to the set of ODEs has been established.", "category": "physics_bio-ph" }, { "text": "Frequency-Dependent Selection at Rough Expanding Fronts: Microbial colonies are experimental model systems for studying the\ncolonization of new territory by biological species through range expansion. We\nstudy a generalization of the two-species Eden model, which incorporates local\nfrequency-dependent selection, in order to analyze how social interactions\nbetween two species influence surface roughness of growing microbial colonies.\nThe model includes several classical scenarios from game theory. We then\nconcentrate on an expanding public goods game, where either cooperators or\ndefectors take over the front depending on the system parameters. We analyze in\ndetail the critical behavior of the nonequilibrium phase transition between\nglobal cooperation and defection and thereby identify a new universality class\nof phase transitions dealing with absorbing states. At the transition, the\nnumber of boundaries separating sectors decays with a novel power law in time\nand their superdiffusive motion crosses over from Eden scaling to a nearly\nballistic regime. In parallel, the width of the front initially obeys Eden\nroughening and, at later times, passes over to selective roughening.", "category": "physics_bio-ph" }, { "text": "Systematic variations in divergence angle: Practical methods for quantitative analysis of radial and angular coordinates\nof leafy organs of vascular plants are presented and applied to published\nphyllotactic patterns of various real systems from young leaves on a shoot tip\nto florets on a flower head. The constancy of divergence angle is borne out\nwith accuracy of less than a degree. It is shown that apparent fluctuations in\ndivergence angle are in large part systematic variations caused by the invalid\nassumption of a fixed center and/or by secondary deformations, while random\nfluctuations are of minor importance.", "category": "physics_bio-ph" }, { "text": "Effects of Ox-LDL on Macrophages NAD(P)H Autofluorescence Changes by\n Two-photon Microscopy: Ox-LDL uptakes by macrophage play a critical role in the happening of\natherosclerosis. Because of its low damage on observed cells and better\nsignal-to- background ratio, two-photon excitation fluorescence microscopy is\nused to observe NAD(P)H autofluorescence of macrophage under difference\ncultured conditions- bare cover glass, coated with fibronectin or\npoly-D-lysine. The results show that the optimal condition is fibronectin\ncoated surface, on which, macrophages profile can be clearly identified on\nNAD(P)H autofluorescence images collected by two-photon microscopy. Moreover,\ndifferent morphology and intensities of autofluorescence under different\nconditions were observed as well. In the future, effects of ox-LDL on\nmacrophages will be investigated by purposed system to research etiology of\natherosclerosis.", "category": "physics_bio-ph" }, { "text": "Front speed in reactive compressible stirred media: We investigated a nonlinear advection-diffusion-reaction equation for a\npassive scalar field. The purpose is to understand how the compressibility can\naffect the front dynamics and the bulk burning rate. We study two classes of\nflows: periodic shear flow and cellular flow both in the case of fast advection\nregime, analysing the system at varying the extent of compressibility and the\nreaction rate. We find that the bulk burning rate in a shear flow increases\nwith compressibility intensity.\n Furthermore, the faster the reaction the more important the difference with\nrespect to the laminar case. The effect has been quantitatively measured and it\nturns out to be generally little. For the cellular flow, the two extreme cases\nhave been investigated, with the whole perturbation situated either in the\ncentre of the vortex or in the periphery. The dependence in this case does not\nshow a monotonic scaling with different behaviour in the two cases. The\nenhancing remains modest and always less than 20%", "category": "physics_bio-ph" }, { "text": "A molecular relay race: sequential first-passage events to the terminal\n reaction centre in a cascade of diffusion controlled processes: We consider a sequential cascade of molecular first-reaction events towards a\nterminal reaction centre in which each reaction step is controlled by diffusive\nmotion of the particles. The model studied here represents a typical reaction\nsetting encountered in diverse molecular biology systems, in which, e.g., a\nsignal transduction proceeds via a series of consecutive \"messengers\": the\nfirst messenger has to find its respective immobile target site triggering a\nlaunch of the second messenger, the second messenger seeks its own target site\nand provokes a launch of the third messenger and so on, resembling a relay race\nin human competitions. For such a molecular relay race taking place in infinite\none-, two- and three-dimensional systems, we find exact expressions for the\nprobability density function of the time instant of the terminal reaction\nevent, conditioned on preceding successful reaction events on an ordered array\nof target sites. The obtained expressions pertain to the most general\nconditions: number of intermediate stages and the corresponding diffusion\ncoefficients, the sizes of the target sites, the distances between them, as\nwell as their reactivities are arbitrary.", "category": "physics_bio-ph" }, { "text": "Unbiased charge oscillations in DNA monomer-polymers and dimer-polymers: We call {\\it monomer} a B-DNA base-pair and examine, analytically and\nnumerically, electron or hole oscillations in monomer- and dimer-polymers,\ni.e., periodic sequences with repetition unit made of one or two monomers. We\nemploy a tight-binding (TB) approach at the base-pair level to readily\ndetermine the spatiotemporal evolution of a single extra carrier along a $N$\nbase-pair polymer. We study HOMO and LUMO eigenspectra as well as the mean over\ntime probabilities to find the carrier at a particular monomer. We use the pure\nmean transfer rate $k$ to evaluate the easiness of charge transfer. The inverse\ndecay length $\\beta$ for exponential fits $k(d)$, where $d$ is the charge\ntransfer distance, and the exponent $\\eta$ for power law fits $k(N)$ are\ncomputed; generally power law fits are better. We illustrate that increasing\nthe number of different parameters involved in the TB description, the fall of\n$k(d)$ or $k(N)$ becomes steeper and show the range covered by $\\beta$ and\n$\\eta$. Finally, both for the time-independent and the time-dependent problem,\nwe analyze the {\\it palindromicity} and the {\\it degree of eigenspectrum\ndependence} of the probabilities to find the carrier at a particular monomer.", "category": "physics_bio-ph" }, { "text": "Physical interactions promote Turing patterns: Turing's mechanism is often invoked to explain periodic patterns in nature,\nalthough direct experimental support is scarce. Turing patterns form in\nreaction-diffusion systems when the activating species diffuse much slower than\nthe inhibiting species, and the involved reactions are highly non-linear. Such\nreactions can originate from co-operativity, whose physical interactions should\nalso affect diffusion. We here take direct interactions into account and show\nthat they strongly affect Turing patterns. We find that weak repulsion between\nthe activator and inhibitor can substantially lower the required differential\ndiffusivity and reaction non-linearity. In contrast, strong interactions can\ninduce phase separation, but the resulting length scale is still typically\ngoverned by the fundamental reaction-diffusion length scale. Taken together,\nour theory connects traditional Turing patterns with chemically active phase\nseparation, thus describing a wider range of systems. Moreover, we demonstrate\nthat even weak interactions affect patterns substantially, so they should be\nincorporated when modeling realistic systems.", "category": "physics_bio-ph" }, { "text": "Bidirectional allostery mechanism of catch-bond effect in cell adhesion: Catch-bonds, whereby noncovalent ligand-receptor interactions are\ncounterintuitively reinforced by tensile forces, play a major role in cell\nadhesion under mechanical stress. A basic prerequisite for catch-bond formation\nis that force-induced remodeling of ligand binding interface occurs prior to\nbond rupture. However, what strategy receptor proteins utilize to meet such\nspecific kinetic control is still unclear, rendering the mechanistic\nunderstanding of catch-bond an open question. Here we report a bidirectional\nallostery mechanism of catch-bond for the hyaluronan (HA) receptor CD44 which\nis responsible for rolling adhesion of lymphocytes and circulating tumor cells.\nBinding of ligand HA allosterically reduces the threshold force for unlocking\nof otherwise stably folded force-sensing element (i.e., forward allostery), so\nthat much smaller tensile force can trigger the conformational switching of\nreceptor protein to high binding-strength state via backward allosteric\ncoupling before bond rupture. The effect of forward allostery was further\nsupported by performing atomistic molecular dynamics simulations. Such\nbidirectional allostery mechanism fulfills the specific kinetic control\nrequired by catch-bond and is likely to be commonly utilized in cell adhesion.\nWe also revealed a slip-catch-slip triphasic pattern in force response of\nCD44-HA bond arising from force-induced repartitioning of parallel dissociation\npathways. The essential thermodynamic and kinetic features of receptor proteins\nfor shaping the catch-bond were identified.", "category": "physics_bio-ph" }, { "text": "A unified approach to the study of temporal, correlational and rate\n coding: We demonstrate that the information contained in the spike occurrence times\nof a population of neurons can be broken up into a series of terms, each of\nwhich reflect something about potential coding mechanisms. This is possible in\nthe coding r{\\'e}gime in which few spikes are emitted in the relevant time\nwindow.\n This approach allows us to study the additional information contributed by\nspike timing beyond that present in the spike counts; to examine the\ncontributions to the whole information of different statistical properties of\nspike trains, such as firing rates and correlation functions; and forms the\nbasis for a new quantitative procedure for the analysis of simultaneous\nmultiple neuron recordings. It also provides theoretical constraints upon\nneural coding strategies. We find a transition between two coding r{\\'e}gimes,\ndepending upon the size of the relevant observation timescale. For time windows\nshorter than the timescale of the stimulus-induced response fluctuations, there\nexists a spike count coding phase, where the purely temporal information is of\nthird order in time. For time windows much longer than the characteristic\ntimescale, there can be additional timing information of first order, leading\nto a temporal coding phase in which timing information may affect the\ninstantaneous information rate.\n We study the relative contributions of the dynamic firing rate and\ncorrelation variables to the full temporal information; the interaction of\nsignal and noise correlations in temporal coding; synergy between spikes and\nbetween cells; and the effect of refractoriness. We illustrate the utility of\nthe technique by analysis of a few cells from the rat barrel cortex.", "category": "physics_bio-ph" }, { "text": "The Heat of Nervous Conduction: A Thermodynamic Framework: Early recordings of nervous conduction revealed a notable thermal signature\nassociated with the electrical signal. The observed production and subsequent\nabsorption of heat arise from physicochemical processes that occur at the cell\nmembrane level during the conduction of the action potential. In particular,\nthe reversible release of electrical energy stored as a difference of potential\nacross the cell membrane appears as a simple yet consistent explanation for the\nheat production, as proposed in the \"Condenser Theory.\" However, the Condenser\nTheory has not been analyzed beyond the analogy between the cell membrane and a\nparallel-plate capacitor, i.e. a condenser, which cannot account for the\nmagnitude of the heat signature. In this work, we use a detailed electrostatic\nmodel of the cell membrane to revisit the Condenser Theory. We derive\nexpressions for free energy and entropy changes associated with the\ndepolarization of the membrane by the action potential, which give a direct\nmeasure of the heat produced and absorbed by neurons. We show how the density\nof surface charges on both sides of the membrane impacts the energy changes.\nFinally, considering a typical action potential, we show that if the membrane\nholds a bias of surface charges, such that the internal side of the membrane is\n0.05 C m$^{-2}$ more negative than the external side, the size of the heat\npredicted by the model reaches the range of experimental values. Based on our\nstudy, we identify the change in electrical energy of the membrane as the\nprimary mechanism of heat production and absorption by neurons during nervous\nconduction.", "category": "physics_bio-ph" }, { "text": "Scatterometry Measurements with Scattered Light Imaging Enable New\n Insights into the Nerve Fiber Architecture of the Brain: The correct reconstruction of individual (crossing) nerve fibers is a\nprerequisite when constructing a detailed network model of the brain. The\nrecently developed technique Scattered Light Imaging (SLI) allows the\nreconstruction of crossing nerve fiber pathways in whole brain tissue samples\nwith micrometer resolution: The individual fiber orientations are determined by\nilluminating unstained histological brain sections from different directions,\nmeasuring the transmitted scattered light under normal incidence, and studying\nthe light intensity profiles of each pixel in the resulting image series. So\nfar, SLI measurements were performed with a fixed polar angle of illumination\nand a small number of illumination directions, providing only an estimate of\nthe nerve fiber directions and limited information about the underlying tissue\nstructure. Here, we use an LED display with individually controllable\nlight-emitting diodes to measure the full distribution of scattered light\nbehind the sample (scattering pattern) for each image pixel at once, enabling\nscatterometry measurements of whole brain tissue samples. We compare our\nresults to coherent Fourier scatterometry (raster-scanning the sample with a\nnon-focused laser beam) and previous SLI measurements with fixed polar angle of\nillumination, using sections from a vervet monkey brain and human optic tracts.\nFinally, we present SLI scatterometry measurements of a human brain section\nwith 3 $\\mu$m in-plane resolution, demonstrating that the technique is a\npowerful approach to gain new insights into the nerve fiber architecture of the\nhuman brain.", "category": "physics_bio-ph" }, { "text": "Mesoscopic model for DNA G-quadruplex unfolding: Genomes contain rare guanine-rich sequences capable of assembling into\nfour-stranded helical structures, termed G-quadruplexes, with potential roles\nin gene regulation and chromosome stability. Their mechanical unfolding has\nonly been reported to date by all-atom simulations, which cannot dissect the\nmajor physical interactions responsible for their cohesion. Here, we propose a\nmesoscopic model to describe both the mechanical and thermal stability of DNA\nG-quadruplexes, where each nucleotide of the structure, as well as each central\ncation located at the inner channel, is mapped onto a single bead. In this\nframework we are able to simulate loading rates similar to the experimental\nones, which are not reachable in simulations with atomistic resolution. In this\nregard, we present single-molecule force-induced unfolding experiments by a\nhigh-resolution optical tweezers on a DNA telomeric sequence capable of forming\na G-quadruplex conformation. Fitting the parameters of the model to the\nexperiments we find a correct prediction of the rupture-force kinetics and a\ngood agreement with previous near equilibrium measurements. Since G-quadruplex\nunfolding dynamics is halfway in complexity between secondary nucleic acids and\ntertiary protein structures, our model entails a nanoscale paradigm for\nnon-equilibrium processes in the cell.", "category": "physics_bio-ph" }, { "text": "Locomotion and proliferation of glioblastoma cells in vitro: statistical\n evaluation of videomicroscopic observations: Long-term videomicroscopy and computer-aided statistical analysis were used\nto determine some characteristic parameters of in vitro cell motility and\nproliferation in three established cell lines derived from human glioblastoma\ntumors. Migration and proliferation activities were compared among the three\ncell lines since these are two features of tumor cells that strongly influence\nthe progression of cancer. The results on these dynamical parameters of cell\nlocomotion were compared to pathological data obtained by traditional methods.\nThe data indicate that the analysis of cell motility provides more specific\ninformation and is potentially useful in diagnosis.", "category": "physics_bio-ph" }, { "text": "DNA-psoralen: single-molecule experiments and first principles\n calculations: The authors measure the persistence and contour lengths of DNA-psoralen\ncomplexes, as a function of psoralen concentration, for intercalated and\ncrosslinked complexes. In both cases, the persistence length monotonically\nincreases until a certain critical concentration is reached, above which it\nabruptly decreases and remains approximately constant. The contour length of\nthe complexes exhibits no such discontinuous behavior. By fitting the relative\nincrease of the contour length to the neighbor exclusion model, we obtain the\nexclusion number and the intrinsic intercalating constant of the psoralen-DNA\ninteraction. Ab initio calculations are employed in order to provide an\natomistic picture of these experimental findings.", "category": "physics_bio-ph" }, { "text": "Noise-induced quantum coherence in photosynthetic complexes with\n multiple energy transfer pathways: We theoretically investigate exciton relaxation dynamics in molecular\naggregates based on model photosynthetic complexes under various conditions of\nincoherent excitation. We show that noise-induced quantum coherence is\ngenerated between spatially-separated exciton states which belong to the same\nor different energy transfer pathways, coupled via real and virtual transfer\nprocesses. Such quantum coherence effects may be used to improve\nlight-harvesting efficiency and to reveal quantum phenomena in biology.", "category": "physics_bio-ph" }, { "text": "Learning Moment Closure in Reaction-Diffusion Systems with Spatial\n Dynamic Boltzmann Distributions: Many physical systems are described by probability distributions that evolve\nin both time and space. Modeling these systems is often challenging to due\nlarge state space and analytically intractable or computationally expensive\ndynamics. To address these problems, we study a machine learning approach to\nmodel reduction based on the Boltzmann machine. Given the form of the reduced\nmodel Boltzmann distribution, we introduce an autonomous differential equation\nsystem for the interactions appearing in the energy function. The reduced model\ncan treat systems in continuous space (described by continuous random\nvariables), for which we formulate a variational learning problem using the\nadjoint method for the right hand sides of the differential equations. This\napproach allows a physical model for the reduced system to be enforced by a\nsuitable parameterization of the differential equations. In this work, the\nparameterization we employ uses the basis functions from finite element\nmethods, which can be used to model any physical system. One application domain\nfor such physics-informed learning algorithms is to modeling reaction-diffusion\nsystems. We study a lattice version of the R{\\\"o}ssler chaotic oscillator,\nwhich illustrates the accuracy of the moment closure approximation made by the\nmethod, and its dimensionality reduction power.", "category": "physics_bio-ph" }, { "text": "A mechanistic perspective on the effect of cholesterol in phospholipid\n bilayers: Cholesterol (CHOL) is one of the most important components of plasma\nmembranes of higher cells and one of the main factors for the formation of\n(nano)domains. In this work, molecular dynamics simulations of mixtures of CHOL\nwith DPPC (saturated lipid) and DLiPC (unsaturated lipid) as standard\nphospholipids (PLs) are presented in a wide range of CHOL concentrations. The\nkey idea is to systematically extract all structural and enthalpic properties\nrelevant to the formulation of a lattice model of these systems and express\nthem in dependence of the acyl chain order parameters. Detailed interpretation\nis simplified by the observation that, to a good approximation, the interaction\neffects do not depend on the total CHOL concentration, but only on the local\nCHOL arrangement. The resulting information can be used to motivate the\nagglomeration of CHOL molecules, the relevance of entropic rather than\nenthalpic effects for understanding the stronger influence of CHOL on DPPC\ncompared to DLiPC, or the thermodynamic background of raft formation. It is\nverified that the interaction functions hardly change during the transition\nfrom binary to ternary mixtures, suggesting the applicability of the concepts\nto more complex mixtures.", "category": "physics_bio-ph" }, { "text": "Giant Negative Mobility of Janus Particles in a Corrugated Channel: We numerically simulate the transport of elliptic Janus particles along\nnarrow two-dimensional channels with reflecting walls. The self-propulsion\nvelocity of the particle is oriented along either their major (prolate) or\nminor axis (oblate). In smooth channels, we observe long diffusion transients:\nballistic for prolate particles and zero-diffusion for oblate particles. Placed\nin a rough channel, prolate particles tend to drift against an applied drive by\ntumbling over the wall protrusions; for appropriate aspect ratios, the modulus\nof their negative mobility grows exceedingly large (giant negative mobility).\nThis suggests that a small external drive suffices to efficiently direct\nself-propulsion of rod-like Janus particles in rough channels.", "category": "physics_bio-ph" }, { "text": "Chromatin and cytoskeletal tethering determine nuclear morphology in\n progerin expressing cells: The nuclear morphology of eukaryotic cells is determined by the interplay\nbetween the lamina forming the nuclear skeleton, the chromatin inside the\nnucleus and the coupling with the cytoskeleton. Nuclear alterations are often\nassociated with pathological conditions as in the Hutchinson-Gilford progeria\nsyndrome (HGPS) where a mutation in the lamin A gene yields an altered form of\nthe protein, named progerin, and an aberrant nuclear shape. Here, we introduce\nan inducible cellular model of HGPS in HeLa cells where increased progerin\nexpression leads to alterations in the coupling of the lamin shell with\ncytoskeletal/chromatin tethers as well as with Polycomb-group (PcG) proteins.\nFurthermore, our experiments show that progerin expression leads to enhanced\nnuclear shape fluctuations in response to cytoskeletal activity. To interpret\nthe experimental results, we introduce a computational model of the cell\nnucleus that includes explicitly chromatin fibers, the nuclear shell and the\ncoupling with the cytoskeleton. The model allows us to investigate how the\ngeometrical organization of chromatin-lamin tether affects nuclear morphology\nand shape fluctuations. In sum, our findings highlight the crucial role played\nby lamin-chromatin and lamin-cytoskeletal alterations in determining nuclear\nshape morphology and in affecting cellular functions and gene regulation.", "category": "physics_bio-ph" }, { "text": "Data-driven classification of individual cells by their non-Markovian\n motion: We present a method to differentiate organisms solely by their motion based\non the generalized Langevin equation (GLE) and use it to distinguish two\ndifferent swimming modes of strongly confined unicellular microalgae\nChlamydomonas reinhardtii (CR). The GLE is the most general model for active or\npassive motion of organisms and particles and in particular includes\nnon-Markovian effects, i.e., the trajectory memory of its past. We extract all\nGLE parameters from individual cell trajectories and perform an unbiased\ncluster analysis to group them into different classes. For the specific cell\npopulation employed in the experiments, the GLE-based assignment into the two\ndifferent swimming modes works perfectly, as checked by control experiments.\nThe classification and sorting of single cells and organisms is important in\ndifferent areas, our method that is based on motion trajectories offers\nwide-ranging applications in biology and medicine.", "category": "physics_bio-ph" }, { "text": "Robust formation of metachronal waves in directional chains of phase\n oscillators: Biological systems can rely on collective formation of a metachronal wave in\nan ensemble of oscillators for locomotion and for fluid transport. We consider\none-dimensional chains of phase oscillators with nearest neighbor interactions,\nconnected in a loop and with rotational symmetry, so each oscillator resembles\nevery other oscillator in the chain. Numerical integrations of the discrete\nphase oscillator systems and a continuum approximation show that directional\nmodels (those that do not obey reversal symmetry), can exhibit instability to\nshort wavelength perturbations but only in regions where the slope in phase has\na particular sign. This causes short wavelength perturbations to develop that\ncan vary the winding number that describes the sum of phase differences across\nthe loop and the resulting metachronal wave speed. Numerical integrations of\nstochastic directional phase oscillator models show that even a weak level of\nnoise can seed instabilities that resolve into metachronal wave states.", "category": "physics_bio-ph" }, { "text": "A new method of brain stimulation at ultra-high frequency: Nerve stimulation via micro-electrode implants is one of the neurostimulation\napproaches which is used frequently in the medical treatment of some brain\ndisorders, neural prosthetics, brain-machine interfaces and also in the cyborg.\nIn this method, the electrical stimulation signal can be categorized by the\nfrequency band: low frequency, high frequency, and ultra-high frequency. The\nstimulation should be less destructive, more smooth, and controllable. In this\narticle, we present a brief description of the mechanism underlying the\nultra-high frequency stimulation. In the flowing, from an informatics\nperspective, we propose a state-of-the-art, low destructive, and highly\nefficient stimulation method at the low amplitude ultra-high frequency signal.\nIn this method, we have tried to reduce the adaptation of the nerve system by\nmodulating the stimulation signal via a low frequency rectangular random wave.\nBy this method, we could reach the \"almost zero discharge\" with minimum\ndestructive effect in the experimental test on the fish nervous system.", "category": "physics_bio-ph" }, { "text": "Ensemble based convergence assessment of biomolecular trajectories: Assessing the convergence of a biomolecular simulation is an essential part\nof any computational investigation. This is because many important quantities\n(e.g., free energy differences) depend on the relative populations of different\nconformers; insufficient convergence translates into systematic errors. Here we\npresent a simple method to self-consistently assess the convergence of a\nsimulation. Standard clustering methods first generate a set of reference\nstructures to any desired precision. The trajectory is then classified by\nproximity to the reference structures, yielding a one-dimensional histogram of\nstructurally distinct populations. Comparing ensembles of different\ntrajectories (or different parts of the same trajectory) built with the same\nreference structures provides a sensitive, quantitative measure of convergence.\nPlease note: this is a preliminary manuscript, and should be read as such.\nComments are most welcome, especially regarding pertinent prior work.", "category": "physics_bio-ph" }, { "text": "Stochastic single-gene auto-regulation: A detailed stochastic model of single-gene auto-regulation is established and\nits solutions are explored when mRNA dynamics is fast compared with protein\ndynamics and in the opposite regime. The model includes all the sources of\nrandomness that are intrinsic to the auto-regulation process and it considers\nboth transcriptional and post transcriptional regulation. The timescale\nseparation allows the derivation of analytic expressions for the equilibrium\ndistributions of protein and mRNA. These distributions are generally well\ndescribed in the continuous approximation, which is used to discuss the\nqualitative features of the protein equilibrium distributions as a function of\nthe biological parameters in the fast mRNA regime. The performance of the\ntimescale approximation is assessed by comparison with simulations of the full\nstochastic system, and a good quantitative agreement is found for a wide range\nof parameter values. We show that either unimodal or bimodal equilibrium\nprotein distributions can arise, and we discuss the auto-regulation mechanisms\nassociated with bimodality.", "category": "physics_bio-ph" }, { "text": "Sequence-Dependent Effects on the Properties of Semiflexible Biopolymers: Using path integral technique, we show exactly that for a semiflexible\nbiopolymer in constant extension ensemble, no matter how long the polymer and\nhow large the external force, the effects of short range correlations in the\nsequence-dependent spontaneous curvatures and torsions can be incorporated into\na model with well-defined mean spontaneous curvature and torsion as well as a\nrenormalized persistence length. Moreover, for a long biopolymer with large\nmean persistence length, the sequence-dependent persistence lengths can be\nreplaced by their mean. However, for a short biopolymer or for a biopolymer\nwith small persistence lengths, inhomogeneity in persistence lengths tends to\nmake physical observables very sensitive to details and therefore less\npredictable.", "category": "physics_bio-ph" }, { "text": "F\u00f6rster resonance energy transfer, absorption and emission spectra in\n multichromophoric systems: I. Cumulant expansions: We study the F\\\"orster resonant energy transfer (FRET) rate in\nmultichromophoric systems. The multichromophoric FRET rate is determined by the\noverlap integral of the donor's emission and acceptor's absorption spectra,\nwhich are obtained via 2nd-order cumulant expansion techniques developed in\nthis work. We calculate the spectra and multichromophoric FRET rate for both\nlocalized and delocalized systems. (i) The role of the initial entanglement\nbetween the donor and its bath is found to be crucial in both the emission\nspectrum and the multichromophoric FRET rate. (ii) The absorption spectra\nobtained by the cumulant expansion method are quite close to the exact one for\nboth localized and delocalized systems, even when the system-bath coupling is\nfar from the perturbative regime. (iii) For the emission spectra, the cumulant\nexpansion can give very good results for the localized system, but fail to\nobtain reliable spectra of the high excitations of a delocalized system, when\nthe system-bath coupling is large and the thermal energy is small. (iv) Even\nthough, the multichromophoric FRET rate is good enough since it is determined\nby the overlap integral of the spectra.", "category": "physics_bio-ph" }, { "text": "Theory of single-molecule experiments in the overstretching force regime: We present a statistical mechanics analysis of the finite-size elasticity of\nbiopolymers, consisting of domains which can exhibit transitions between more\nthan one stable state at large applied force. The constant-force (Gibbs) and\nconstant-displacement (Helmholtz) formulations of single molecule stretching\nexperiments are shown to converge in the thermodynamic limit. Monte Carlo\nsimulations of continuous three dimensional polymers of variable length are\ncarried out, based on this formulation. We demonstrate that the experimental\nforce-extension curves for short and long chain polymers are described by a\nunique universal model, despite the differences in chemistry and\nrate-dependence of transition forces.", "category": "physics_bio-ph" }, { "text": "Nonlinear DNA dynamics: nonlinearity versus dispersion: In the present paper we study the impact of dispersion and nonlinearity on\nDNA dynamics. We rely on the helicoidal Peyrard-Bishop model and use the fact\nthat nonlinear DNA dynamics represents an interplay between nonlinearity and\ndispersion. We state that a dispersion coefficient and a coefficient of\nnonlinearity, existing in nonlinear Schr\\\"odinger equation, are mutually\ndependent and show how function and can be obtained. Also, we show how all this\ncan be used to find a possible interval for the parameter describing helicoidal\nstructure of DNA.", "category": "physics_bio-ph" }, { "text": "Mode Localization in the Cooperative Dynamics of Protein Recognition: The biological function of proteins is encoded in their structure and\nexpressed through the mediation of their dynamics. Local fluctuations are known\nto initiate biologically relevant pathways as they cooperatively enhance the\ndynamics in specific regions in the protein. Those biologically active regions\nprovide energetically-comparable conformational states that can be trapped by a\nreacting partner. We analyze this mechanism as we calculate the dynamics of\nmonomeric and dimerized HIV protease, and free Insulin Growth Factor II\nReceptor (IGF2R) domain 11 and its IGF2R:IGF2 complex. We adopt a newly\ndeveloped coarse-grained model, the Langevin Equation for Protein Dynamics\n(LE4PD), which predicts dynamical relevant mechanisms with high accuracy. Both\nsimulation-derived and experimental NMR conformers are the input structural\nensembles for the LE4PD. The use of the experimental NMR conformers requires\nminimal computational resources.", "category": "physics_bio-ph" }, { "text": "Application of magnetically induced hyperthermia on the model protozoan\n Crithidia fasciculata as a potential therapy against parasitic infections: Magnetic hyperthermia is currently an EU-approved clinical therapy against\ntumor cells that uses magnetic nanoparticles under a time varying magnetic\nfield (TVMF). The same basic principle seems promising against trypanosomatids\ncausing Chagas disease and sleeping sickness, since therapeutic drugs available\ndisplay severe side effects and drug-resistant strains. However, no\napplications of this strategy against protozoan-induced diseases have been\nreported so far. In the present study, Crithidia fasciculata, a widely used\nmodel for therapeutic strategies against pathogenic trypanosomatids, was\ntargeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotely\nprovoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nm\nwere synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPs\nwere added to Crithidia fasciculata choanomastigotes in exponential phase and\nincubated overnight. The amount of uploaded MNPs per cell was determined by\nmagnetic measurements. Cell viability using the MTT colorimetric assay and flow\ncytometry showed that the MNPs were incorporated by the cells with no\nnoticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) was\napplied to MNP-bearing cells, massive cell death was induced via a\nnon-apoptotic mechanism. No effects were observed by applying a TVMF on control\n(without loaded MNPs) cells. No macroscopic rise in temperature was observed in\nthe extracellular medium during the experiments. Scanning Electron Microscopy\nshowed morphological changes after TVMF experiments. These data indicate (as a\nproof of principle) that intracellular hyperthermia is a suitable technology to\ninduce the specific death of protozoan parasites bearing MNPs. These findings\nexpand the possibilities for new therapeutic strategies that combat parasitic\ninfections.", "category": "physics_bio-ph" }, { "text": "A phenomenological operator description of interactions between\n populations with applications to migration: We adopt an operatorial method based on the so-called creation, annihilation\nand number operators in the description of different systems in which two\npopulations interact and move in a two-dimensional region. In particular, we\ndiscuss diffusion processes modeled by a quadratic hamiltonian. This general\nprocedure will be adopted, in particular, in the description of migration\nphenomena. With respect to our previous analogous results, we use here\nfermionic operators since they automatically implement an upper bound for the\npopulation densities.", "category": "physics_bio-ph" }, { "text": "Optimal noise maximizes collective motion in heterogeneous media: We study the effect of spatial heterogeneity on the collective motion of\nself-propelled particles (SPPs). The heterogeneity is modeled as a random\ndistribution of either static or diffusive obstacles, which the SPPs avoid\nwhile trying to align their movements. We find that such obstacles have a\ndramatic effect on the collective dynamics of usual SPP models. In particular,\nwe report about the existence of an optimal (angular) noise amplitude that\nmaximizes collective motion. We also show that while at low obstacle densities\nthe system exhibits long-range order, in strongly heterogeneous media\ncollective motion is quasi-long-range and exists only for noise values in\nbetween two critical noise values, with the system being disordered at both,\nlarge and low noise amplitudes. Since most real system have spatial\nheterogeneities, the finding of an optimal noise intensity has immediate\npractical and fundamental implications for the design and evolution of\ncollective motion strategies.", "category": "physics_bio-ph" }, { "text": "Molecular dynamics simulations of a single stranded (ss) DNA: The objective of the present study was to develop an understanding of short\nsingle-stranded DNA (ssDNA) to assist the development of new DNA-based\nbiosensors. A ssDNA model containing twelve bases was constructed from the\n130-145 codon sequence of the p53 gene. Various thermodynamic macroscopic\nobservables such as temperature, energy distributions, as well as root mean\nsquare deviation (RMSD) of the nucleic acid backbone of the ssDNA were studied\nusing molecular dynamics (MD) simulations. The AMBER program was used for\nbuilding the structural model of the ssDNA, and atomistic MD simulations in\nthree different ensembles were carried out using the NAMD program. The\nmicrocanonical (NVE), conical (NVT) and isobaric-isothermal (NPT) ensembles\nwere employed to compare the equilibrium characteristics of ssDNA in aqueous\nsolutions. Our results indicate that the conformational stability of the ssDNA\nis dependent on the thermodynamic conditions.", "category": "physics_bio-ph" }, { "text": "Adaptive sampling by information maximization: The investigation of input-output systems often requires a sophisticated\nchoice of test inputs to make best use of limited experimental time. Here we\npresent an iterative algorithm that continuously adjusts an ensemble of test\ninputs online, subject to the data already acquired about the system under\nstudy. The algorithm focuses the input ensemble by maximizing the mutual\ninformation between input and output. We apply the algorithm to simulated\nneurophysiological experiments and show that it serves to extract the ensemble\nof stimuli that a given neural system ``expects'' as a result of its natural\nhistory.", "category": "physics_bio-ph" }, { "text": "Self-Organizing Approach for Finding Borders of DNA Coding Regions: A self-organizing approach is proposed for gene finding based on the model of\ncodon usage for coding regions and positional preference for noncoding regions.\nThe symmetry between the direct and reverse coding regions is adopted for\nreducing the number of parameters. Without requiring prior training, parameters\nare estimated by iteration. By employing the window sliding technique and\nlikelihood ratio, a very accurate segmentation is obtained.", "category": "physics_bio-ph" }, { "text": "Non-invasive lipid quantification of living microalgal cultures with\n digital holographic microscopy: Some microalgae store large amounts of neutral lipids inside lipid droplets.\nSince these lipids can be used to produce biodiesel in a sustainable way,\nresearch is developing on fast non-destructive methods to quantify and monitor\nthe amount of lipids in microalgal cultures. In this paper, we have developed\nwith digital holographic microscopy a fast quantitative method to assess the\nevolution of the lipid content inside the diatom Phaeodactylum tricornutum\nliving cells. The method uses a specific processing of recorded hologram\nsequences based on the refocusing capability of digital holographic microscopy.\nEach lipid droplet volume is evaluated inside the cells on representative\nsamples of the culture. We have validated the method thanks to correlative\nquantitative phase contrast-fluorescence imaging and extrapolated it to larger\ncalibrated spherical refractive particles, to demonstrate the flexibility of\nthe method.", "category": "physics_bio-ph" }, { "text": "Multimodal Analysis of Traction Forces and Temperature Dynamics of\n Living Cells with Diamond-Embedded Substrate: Cells and tissues are constantly exposed to various chemical and physical\nsignals that intricately regulate various physiological and pathological\nprocesses. This study explores the integration of two biophysical methods,\nTraction Force Microscopy (TFM) and Optically-Detected Magnetic Resonance\n(ODMR), to concurrently assess cellular traction forces and local relative\ntemperature. We present a novel elastic substrate with embedded\nnitrogen-vacancy microdiamonds, that facilitate ODMR-TFM measurements.\nOptimization efforts have focused on minimizing the sample illumination and\nexperiment duration to mitigate biological perturbations. Our hybrid ODMR-TFM\ntechnique yields precise TFM maps and achieves approximately 1K accuracy in\nrelative temperature measurements. Notably, our setup, employing a simple\nwide-field fluorescence microscope with standard components, demonstrates the\nbroader feasibility of these techniques in life-science laboratories. By\nelucidating the physical aspects of cellular behavior beyond the existing\nmethods, this approach opens avenues for a deeper understanding and may inspire\ndiverse biomedical applications.", "category": "physics_bio-ph" }, { "text": "Mechanics of allostery: contrasting the induced fit and population shift\n scenarios: In allosteric proteins, binding a ligand can affect function at a distant\nlocation, for example by changing the binding affinity of a substrate at the\nactive site. The induced fit and population shift models, which differ by the\nassumed number of stable configurations, explain such cooperative binding from\na thermodynamic viewpoint. Yet, understanding what mechanical principles\nconstrain these models remains a challenge. Here we provide an empirical study\non 34 proteins supporting the idea that allosteric conformational change\ngenerally occurs along a soft elastic mode presenting extended regions of high\nshear. We argue, based on a detailed analysis of how the energy profile along\nsuch a mode depends on binding, that in the induced fit scenario there is an\noptimal stiffness $k_a^*\\sim 1/N$ for cooperative binding, where $N$ is the\nnumber of residues involved in the allosteric response. We find that the\npopulation shift scenario is more robust to mutation affecting stiffness, as\nbinding becomes more and more cooperative with stiffness up to the same\ncharacteristic value $k_a^*$, beyond which cooperativity saturates instead of\ndecaying. We confirm numerically these findings in a non-linear mechanical\nmodel. Dynamical considerations suggest that a stiffness of order $k_a^*$ is\nfavorable in that scenario as well, supporting that for proper function\nproteins must evolve a functional elastic mode that is softer as their size\nincreases. In consistency with this view, we find a significant anticorrelation\nbetween the stiffness of the allosteric response and protein size in our data\nset.", "category": "physics_bio-ph" }, { "text": "Metastable Chimera States in Community-Structured Oscillator Networks: A system of symmetrically coupled identical oscillators with phase lag is\npresented, which is capable of generating a large repertoire of transient\n(metastable) \"chimera\" states in which synchronisation and desynchronisation\nco-exist. The oscillators are organised into communities, such that each\noscillator is connected to all its peers in the same community and to a subset\nof the oscillators in other communities. Measures are introduced for\nquantifying metastability, the prevalence of chimera states, and the variety of\nsuch states a system generates. By simulation, it is shown that each of these\nmeasures is maximised when the phase lag of the model is close, but not equal,\nto pi/2. The relevance of the model to a number of fields is briefly discussed,\nwith particular emphasis on brain dynamics.", "category": "physics_bio-ph" }, { "text": "Coupled Two-Way Clustering Analysis of Gene Microarray Data: We present a novel coupled two-way clustering approach to gene microarray\ndata analysis. The main idea is to identify subsets of the genes and samples,\nsuch that when one of these is used to cluster the other, stable and\nsignificant partitions emerge. The search for such subsets is a computationally\ncomplex task: we present an algorithm, based on iterative clustering, which\nperforms such a search. This analysis is especially suitable for gene\nmicroarray data, where the contributions of a variety of biological mechanisms\nto the gene expression levels are entangled in a large body of experimental\ndata. The method was applied to two gene microarray data sets, on colon cancer\nand leukemia. By identifying relevant subsets of the data and focusing on them\nwe were able to discover partitions and correlations that were masked and\nhidden when the full dataset was used in the analysis. Some of these partitions\nhave clear biological interpretation; others can serve to identify possible\ndirections for future research.", "category": "physics_bio-ph" }, { "text": "Principles for sensitive and robust biomolecular interaction analysis -\n The limits of detection and resolution of diffraction-limited focal\n molography: Label-free biosensors enable the monitoring of biomolecular interactions in\nreal-time, which is key to the analysis of the binding characteristics of\nbiomolecules. While refractometric optical biosensors are sensitive and\nwell-established, they are susceptible to any change of the refractive index in\nthe sensing volume caused by minute variations in composition of the sample\nbuffer, temperature drifts and nonspecific binding to the sensor surface.\nRefractometric biosensors require reference channels as well as temperature\nstabilisation and their applicability in complex fluids such as blood is\nlimited by nonspecific bindings. Focal molography does not measure the\nrefractive index of the entire sensing volume but detects the diffracted light\nfrom a coherent assembly of analyte molecules. Thus, it does not suffer from\nthe limitations of refractometric sensors since they stem from non-coherent\nprocesses and therefore do not add to the coherent molographic signal. The\ncoherent assembly is generated by selective binding of the analyte molecules to\na synthetic binding pattern - the mologram. Focal Molography has been\nintroduced theoretically and verified experimentally in previous papers.\nHowever, further understanding of the underlying physics and a\ndiffraction-limited readout is needed to unveil its full potential. This paper\nintroduces refined theoretical models which can accurately quantify the amount\nof matter bound to the mologram from the diffracted intensity. In addition, it\npresents measurements of diffraction-limited molographic foci. These\nimprovements enabled us to demonstrate a resolution in real-time binding\nexperiments comparable to the best SPR sensors, without the need of temperature\nstabilisation or drift correction and to detect small molecules label-free in\nan endpoint format. The presented experiments exemplify the robustness and\nsensitivity of diffractometric sensors.", "category": "physics_bio-ph" }, { "text": "DNA Dynamics in A Water Drop: Due to its polyionic character the DNA double helix is stable and\nbiologically active only in salty aqueous media where its charge is compensated\nby solvent counterions. Monovalent metal ions are ubiquitous in DNA environment\nand they are usually considered as the possible driving force of\nsequence-dependent modulations of DNA structure that make it recognizable by\nproteins. In an effort to directly examine this hypothesis, MD simulations of\nDNA in a water drop surrounded by vacuum were carried out, which relieves the\nrequirement of charge neutrality. Surprisingly, with zero concentration of\ncounterions a dodecamer DNA duplex appears metastable and its structure remains\nsimilar to that observed in experiments.", "category": "physics_bio-ph" }, { "text": "Aggregation of self-propelled particles with sensitivity to local order: We study a system of self-propelled particles (SPPs) in which individual\nparticles are allowed to switch between a fast aligning and a slow nonaligning\nstate depending upon the degree of the alignment in the neighborhood. The\nswitching is modeled using a threshold for the local order parameter. This\nadditional attribute gives rise to a mixed phase, in contrast to the ordered\nphases found in clean SPP systems. As the threshold is increased from zero, we\nfind the sudden appearance of clusters of nonaligners. Clusters of nonaligners\ncoexist with moving clusters of aligners with continual coalescence and\nfragmentation. The behavior of the system with respect to the clustering of\nnonaligners appears to be very different for values of low and high global\ndensities. In the low density regime, for an optimal value of the threshold,\nthe largest cluster of nonaligners grows in size up to a maximum that varies\nlogarithmically with the total number of particles. However, on further\nincreasing the threshold the size decreases. In contrast, for the high density\nregime, an initial abrupt rise is followed by the appearance of a giant cluster\nof nonaligners. The latter growth can be characterized as a continuous\npercolation transition. In addition, we find that the speed differences between\naligners and nonaligners is necessary for the segregation of aligners and\nnonaligners.", "category": "physics_bio-ph" }, { "text": "Modeling symbiosis by interactions through species carrying capacities: We introduce a mathematical model of symbiosis between different species by\ntaking into account the influence of each species on the carrying capacities of\nthe others. The modeled entities can pertain to biological and ecological\nsocieties or to social, economic and financial societies. Our model includes\nthree basic types: symbiosis with direct mutual interactions, symbiosis with\nasymmetric interactions, and symbiosis without direct interactions. In all\ncases, we provide a complete classification of all admissible dynamical\nregimes. The proposed model of symbiosis turned out to be very rich, as it\nexhibits four qualitatively different regimes: convergence to stationary\nstates, unbounded exponential growth, finite-time singularity, and finite-time\ndeath or extinction of species.", "category": "physics_bio-ph" }, { "text": "Developing Mathematics for Insight into Sensorimotor Neurobiology: This paper summarizes a research program to express the organization of\nsensorimotor control by specifying physiological states and the conditions for\ntransitions among them. By a slight change in standard notation, conditional\ndynamics provides a moving spotlight, focussing on salient subspaces within a\nhigh-dimensional space. This mathematical approach serves as a window on the\norganization of sensorimotor neurobiology. The intertwined efforts to express\nthe intrinsic organization of neurobiology and to clarify it mathematically are\nyielding a mathematical structure that is growing on fertile empirical ground.", "category": "physics_bio-ph" }, { "text": "On axoplasmic pressure waves and their possible role in nerve impulse\n propagation: It is suggested that the propagation of the action potential is accompanied\nby an axoplasmic pressure pulse propagating in the axoplasm along the axon\nlength. The pressure pulse stretch-modulates voltage-gated Na (Nav) channels\nembedded in the axon membrane, causing their accelerated activation and\ninactivation and increasing peak channel conductance. As a result, the action\npotential propagates due to mechano-electrical activation of Nav channels by\nstraggling ionic currents and the axoplasmic pressure pulse. The velocity of\nsuch propagation is higher than in the classical purely electrical Nav\nactivation mechanism, and it may be close to the velocity of propagation of\npressure pulses in the axoplasm. Extracellular Ca ions influxing during the\nvoltage spike, or Ca ions released from intracellular stores, may trigger a\nmechanism that generates and augments the pressure pulse, thus opposing its\nviscous decay. The model can potentially explain a number of phenomena that are\nnot contained within the purely electrical Hodgkin-Huxley-type framework: the\nMeyer-Overton rule for the effectiveness of anesthetics, as well as various\nmechanical, optical and thermodynamic phenomena accompanying the action\npotential. It is shown that the velocity of propagation of axoplasmic pressure\npulses is close to the measured velocity of the nerve impulse, both in absolute\nmagnitude and in dependence on axon diameter, degree of myelination and\ntemperature.", "category": "physics_bio-ph" }, { "text": "Temperature and force dependence of nanoscale electron transport via the\n Cu protein Azurin: The mechanisms of solid-state electron transport (ETp) via a monolayer of\nimmobilized Azurin (Az) was examined by conducting probe atomic force\nmicroscopy (CP-AFM), both as function of temperature (248 - 373K) and of\napplied tip force (6-12 nN). By varying both temperature and force in CP-AFM,\nwe find that the ETp mechanism can alter with a change in the force applied via\nthe tip to the proteins. As the applied force increases, ETp via Az changes\nfrom temperature-independent to thermally activated at high temperatures. This\nis in contrast to the Cu-depleted form of Az (apo-Az), where increasing the\napplied force causes only small quantitative effects, that fit with a decrease\nin electrode spacing. At low force ETp via holo-Az is temperature-independent\nand thermally activated via apo-Az. This observation agrees with\nmacroscopic-scale measurements, thus confirming that the difference in ETp\ndependence on temperature between holo- and apo-Az is an inherent one that may\nreflect a difference in rigidity between the two forms. An important\nimplication of these results, which depend on CP-AFM measurements over a\nsignificant temperature range, is that for ETp measurements on floppy systems,\nsuch as proteins, the stress applied to the sample should be kept constant or,\nat least controlled during measurement.", "category": "physics_bio-ph" }, { "text": "Scale-free dynamics of somatic adaptability in immune system: The long-time dynamics of somatic adaptability in immune system is simulated\nby a simple physical model. The immune system described by the model exhibits a\nscale free behavior as is observed in living systems. The balance between the\npositive and negative feedbacks of the model leads to a robust immune system\nwhere the positive one corresponds to the formation of memory cells and the\nnegative one to immunosuppression. Also the immunosenescence of the system is\ndiscussed based on the time-dependence of the epigenetic landscape of the\nadaptive immune cells in the shape space.", "category": "physics_bio-ph" }, { "text": "Computational design of antimicrobial active surfaces via automated\n Bayesian optimization: Biofilms pose significant problems for engineers in diverse fields, such as\nmarine science, bioenergy, and biomedicine, where effective biofilm control is\na long-term goal. The adhesion and surface mechanics of biofilms play crucial\nroles in generating and removing biofilm. Designing customized nano-surfaces\nwith different surface topologies can alter the adhesive properties to remove\nbiofilms more easily and greatly improve long-term biofilm control. To rapidly\ndesign such topologies, we employ individual-based modeling and Bayesian\noptimization to automate the design process and generate different active\nsurfaces for effective biofilm removal. Our framework successfully generated\nideal nano-surfaces for biofilm removal through applied shear and vibration.\nDensely distributed short pillar topography is the optimal geometry to prevent\nbiofilm formation. Under fluidic shearing, the optimal topography is to\nsparsely distribute tall, slim, pillar-like structures. When subjected to\neither vertical or lateral vibrations, thick trapezoidal cones are found to be\noptimal. Optimizing the vibrational loading indicates a small vibration\nmagnitude with relatively low frequencies is more efficient in removing\nbiofilm. Our results provide insights into various engineering fields that\nrequire surface-mediated biofilm control. Our framework can also be applied to\nmore general materials design and optimization.", "category": "physics_bio-ph" }, { "text": "Broad pore lifetime distributions: A fundamental concept for cell\n electroporation: We describe a concept that has the potential to change how we think about the\nunderlying mechanisms of cell membrane electroporation (EP). Prior\nexperimental, theoretical and modeling have emphasized a single pore lifetime\nas adequate for particular conditions. Here we introduce a much more complex\nresponse: The rapid creation of many types of pore structures, of which some\nare traditional transient lipidic pores (TPs), but the great majority are\ncomplex pores (CPs) based on both lipids and other molecules or molecular\nsegments. At the inner leaflet of the cell plasma membrane (PM) non-lipidic\nmolecules come from the over-crowded cytoplasm. At the outer leaflet they\noriginate from the extracellular medium and extracellular matrix. Some\npartially or fully insert into TPs during or shortly after TP formation, or\nbind to the membrane nearby. This process is complex, leading to mostly\nshort-lived structures, with relatively few lasting for long times. We\nspeculate that the characteristic pore lifetimes range from $\\sim$100 ns to\n1,000 s, based on implications from experiments. The frequency-of-occurrence\nprobably falls off extremely rapidly with increasing lifetime, $\\tau_{CP}$,\nwhich implies that most are inaccessible to traditional experimental methods.\nIt also suggests that unexpected behavior can occur early in pulsing, vanishing\nbefore post-pulse observations begin.", "category": "physics_bio-ph" }, { "text": "On scaling laws at the phase transition of systems with divergent order\n parameter and/or internal length : the example of DNA denaturation: We used the Transfer-Integral method to compute, with an uncertainty smaller\nthan 5%, the six fundamental characteristic exponents of two dynamical models\nfor DNA thermal denaturation and investigate the validity of the scaling laws.\nDoubts concerning this point arise because the investigated systems (i) have a\ndivergent internal length, (ii) are described by a divergent order parameter,\n(iii) are of dimension 1. We found that the assumption that the free energy can\nbe described by a single homogeneous function is robust, despite the divergence\nof the order parameter, so that Rushbrooke's and Widom's identities are valid\nrelations. Josephson's identity is instead not satisfied. This is probably due\nto the divergence of the internal length, which invalidates the assumption that\nthe correlation length is solely responsible for singular contributions to\nthermodynamic quantities. Fisher's identity is even wronger. We showed that\nthis is due to the d=1 dimensionality and obtained an alternative law, which is\nwell satisfied at DNA thermal denaturation.", "category": "physics_bio-ph" }, { "text": "From jamming to collective cell migration through a boundary induced\n transition: Cell monolayers provide an interesting example of active matter, exhibiting a\nphase transition from a flowing to jammed state as they age. Here we report\nexperiments and numerical simulations illustrating how a jammed cellular layer\nrapidly reverts to a flowing state after a wound. Quantitative comparison\nbetween experiments and simulations shows that cells change their\nself-propulsion and alignement strength so that the system crosses a phase\ntransition line, which we characterize by finite-size scaling in an active\nparticle model. This wound-induced unjamming transition is found to occur\ngenerically in epithelial, endothelial and cancer cells.", "category": "physics_bio-ph" }, { "text": "Point-like inclusion interactions in tubular membranes: We analytically study membrane mediated interactions between inclusions\nembedded in a tubular membrane. We model inclusions as constraints coupled to\nthe curvature tensor of the membrane tube. First, as special test cases, we\nanalyze the interaction between ring and rod shaped inclusions. Using Monte\nCarlo simulations, we further show how point-like inclusions interact to form\nlinear aggregates. Our results reveal that depending on the hard-core radius of\nthe inclusions, they arrange into either lines or rings to globally minimize\nthe curvature energy of the membrane.", "category": "physics_bio-ph" }, { "text": "Emission of Mitochondrial Biophotons and their Effect on Electrical\n Activity of Membrane via Microtubules: In this paper we argue that, in addition to electrical and chemical signals\npropagating in the neurons of the brain, signal propagation takes place in the\nform of biophoton production. This statement is supported by recent\nexperimental confirmation of photon guiding properties of a single neuron. We\nhave investigated the interaction of mitochondrial biophotons with microtubules\nfrom a quantum mechanical point of view. Our theoretical analysis indicates\nthat the interaction of biophotons and microtubules causes\ntransitions/fluctuations of microtubules between coherent and incoherent\nstates. A significant relationship between the fluctuation function of\nmicrotubules and alpha-EEG diagrams is elaborated on in this paper. We argue\nthat the role of biophotons in the brain merits special attention.", "category": "physics_bio-ph" }, { "text": "Successes and failures of simple statistical physics models for a\n network of real neurons: Biological networks exhibit complex, coordinated patterns of activity. Can\nthese patterns be captured precisely in simple models? Here we use measurements\nof simultaneous activity in 1000+ neurons in the mouse brain to test the\nvalidity of models grounded in statistical physics. When cells are dense\nsamples from a small region, we find extremely detailed quantitative agreement\nbetween theory and experiment; sparse samples from larger regions lead to model\nfailures. These results show we can aspire to more than qualitative agreement\nbetween simplifying theoretical ideas and the detailed behavior of a complex\nbiological system.", "category": "physics_bio-ph" }, { "text": "pH Sensing by Lipids in Membranes: The Fundamentals of pH-driven\n Migration, Polarization and Deformations of Lipid Bilayer Assemblies: Most biological molecules contain acido-basic groups that modulate their\nstructure and interactions. A consequence is that pH gradients, local\nheterogeneities and dynamic variations are used by cells and organisms to drive\nor regulate specific biological functions including energetic metabolism,\nvesicular traffic, migration and spatial patterning of tissues in development.\nWhile the direct or regulatory role of pH in protein function is well\ndocumented, the role of hydrogen and hydroxyl ions in modulating the properties\nof lipid assemblies such as bilayer membranes is only beginning to be\nunderstood. Here, we review approaches using artificial lipid vesicles that\nhave been instrumental in providing an understanding of the influence of pH\ngradients and local variations on membrane vectorial motional processes:\nmigration, membrane curvature effects promoting global or local deformations,\ncrowding generation by segregative polarization processes. In the case of pH\ninduced local deformations, an extensive theoretical framework is given and an\napplication to a specific biological issue, namely the structure and stability\nof mitochondrial cristae, is described.", "category": "physics_bio-ph" }, { "text": "A structure-based model fails to probe the mechanical unfolding pathways\n of the titin I27 domain: We discuss the use of a structure based C$\\alpha$-Go model and Langevin\ndynamics to study in detail the mechanical properties and unfolding pathway of\nthe titin I27 domain. We show that a simple Go-model does detect correctly the\norigin of the mechanical stability of this domain. The unfolding free energy\nlandscape parameters $x_u$ and $\\Delta G^{\\ddagger}$, extracted from\ndependencies of unfolding forces on pulling speeds, are found to agree\nreasonably well with experiments. We predict that above $v=10^4$ nm/s the\nadditional force-induced intermediate state is populated at an end-to-end\nextension of about $75 \\mathring{A}$. The force-induced switch in the unfolding\npathway occurs at the critical pulling speed $v_{crit} \\approx 10^6-10^7$ nm/s.\nWe argue that this critical pulling speed is an upper limit of the interval\nwhere Bell's theory works. However, our results suggest that the Go-model fails\nto reproduce the experimentally observed mechanical unfolding pathway properly,\nyielding an incomplete picture of the free energy landscape. Surprisingly, the\nexperimentally observed intermediate state with the A strand detached is not\npopulated in Go-model simulations over a wide range of pulling speeds. The\ndiscrepancy between simulation and experiment is clearly seen from the early\nstage of the unfolding process which shows the limitation of the Go model in\nreproducing unfolding pathways and deciphering the complete picture of the free\nenergy landscape.", "category": "physics_bio-ph" }, { "text": "IR-Laser Welding and Ablation of Biotissue Stained with Metal\n Nanoparticles: In the present work we have studied the possibility of laser welding and\nablation of biological tissue by the using of spherical metal nanoparticles\n(NPs) and infrared laser irradiation which spectrally located far from plasmon\nresonances. YAG:Nd laser with 1064 nm wavelength, 8 ns pulse duration, and\noperating in transverse electromagnetic modes TEM$_{00}$ was used for the\nsynthesis of metal NPs. The Au,Ti Ni and Cu as well as Au-Ag and Au-Cu hybrid\nmetal NPs were formed in the liquid medium. Effectiveness of laser ablation in\nthe case of the biotissue sample that stained with the metal NPs was\napproximately on 4-5 times larger than for the native sample. Also the scheme\nof a laser point welding for the deep-located biotissue layer selectively\nstained by the metal NPs has been demonstrated.", "category": "physics_bio-ph" }, { "text": "Entrainment of heterogeneous glycolytic oscillations in single cells: Cell signaling, gene expression, and metabolism are affected by cell-cell\nheterogeneity and random changes in the environment. The effects of such\nfluctuations on cell signaling and gene expression have recently been studied\nintensively using single-cell experiments. In metabolism heterogeneity may be\nparticularly important because it may affect synchronisation of metabolic\noscillations, an important example of cell-cell communication. This\nsynchronisation is notoriously difficult to describe theoretically as the\nexample of glycolytic oscillations shows: neither is the mechanism of\nglycolytic synchronisation understood nor the role of cell-cell heterogeneity.\nTo pin down the mechanism and to assess its robustness and universality we have\nexperimentally investigated the entrainment of glycolytic oscillations in\nindividual yeast cells by periodic external perturbations. We find that\noscillatory cells synchronise through phase shifts and that the mechanism is\ninsensitive to cell heterogeneity (robustness) and similar for different types\nof external perturbations (universality).", "category": "physics_bio-ph" }, { "text": "Influence of fluctuations in actin structure on myosin V step size: We study the influence of disorder in the helical actin structure on the\nmyosin V step size, predicted from the elastic lever arm model. We show that\nfluctuations of +-5 degrees per actin subunit, as proposed by Egelman et al.,\nsignificantly alter the distribution of step sizes and improve the agreement\nwith experimental data.", "category": "physics_bio-ph" }, { "text": "Disentangling electronic and vibronic coherences in two-dimensional echo\n spectra: The prevalence of long-lasting oscillatory signals in the 2d\necho-spectroscopy of light-harvesting complexes has led to a search for\npossible mechanisms. We investigate how two causes of oscillatory signals are\nintertwined: (i) electronic coherences supporting delocalized wave-like motion,\nand (ii) narrow bands in the vibronic spectral density. To disentangle the\nvibronic and electronic contributions we introduce a time-windowed Fourier\ntransform of the signal amplitude. We find that 2d spectra can be dominated by\nexcitations of pathways which are absent in excitonic energy transport. This\nleads to an underestimation of the life-time of electronic coherences by 2d\nspectra.", "category": "physics_bio-ph" }, { "text": "Polarized interfacial tension induces collective migration of cells, as\n a cluster, in a three-dimensional tissue: Cells collectively migrate as a cluster in three-dimensional (3D) tissues,\nsuch as in embryogenesis and cancer invasion. Here, numerical simulations using\na 3D vertex model show that polarized interfacial tension, expressing cell\nadhesion and cortex contractility, induces the cluster migration in the 3D\nspace. The mechanism is that polarized interfacial tension induced a\ndirectional flow of cell-cell interfaces from the front to rear within the\nwhole cluster, producing a driving force, i.e., cells move forward as a cluster\nby simply expanding and contracting cell-cell boundaries.", "category": "physics_bio-ph" }, { "text": "Kinetic and hydrodynamic models of chemotactic aggregation: We derive general kinetic and hydrodynamic models of chemotactic aggregation\nthat describe certain features of the morphogenesis of biological colonies\n(like bacteria, amoebae, endothelial cells or social insects). Starting from a\nstochastic model defined in terms of N coupled Langevin equations, we derive a\nnonlinear mean field Fokker-Planck equation governing the evolution of the\ndistribution function of the system in phase space. By taking the successive\nmoments of this kinetic equation and using a local thermodynamic equilibrium\ncondition, we derive a set of hydrodynamic equations involving a damping term.\nIn the limit of small frictions, we obtain a hyperbolic model describing the\nformation of network patterns (filaments) and in the limit of strong frictions\nwe obtain a parabolic model which is a generalization of the standard\nKeller-Segel model describing the formation of clusters (clumps). Our approach\nconnects and generalizes several models introduced in the chemotactic\nliterature. We discuss the analogy between bacterial colonies and\nself-gravitating systems and between the chemotactic collapse and the\ngravitational collapse (Jeans instability). We also show that the basic\nequations of chemotaxis are similar to nonlinear mean field Fokker-Planck\nequations so that a notion of effective generalized thermodynamics can be\ndeveloped.", "category": "physics_bio-ph" }, { "text": "Motility-induced phase separation of active particles in the presence of\n velocity alignment: Self-propelled particle (SPP) systems are intrinsically out of equilibrium\nsystems, where each individual particle converts energy into work to move in a\ndissipative medium. When interacting through a velocity alignment mechanism,\nand the medium acts as a momentum sink, even momentum is not conserved. In this\nscenario, a mapping into an equilibrium system seems unlikely. Here, we show\nthat an entropy functional can be derived for SPPs with velocity alignment and\ndensity-dependent speed, at least in the (orientationally) disordered phase.\nThis non-trivial result has important physical consequences. The study of the\nentropy functional reveals that the system can undergo phase separation before\nthe orientational-order phase transition known to occur in SPP systems with\nvelocity alignment.Moreover, we indicate that the spinodal line is a function\nof the alignment sensitivity and show that density fluctuations as well as the\ncritical spatial diffusion, that leads to phase separation, dramatically\nincrease as the orientational-order transition is approached.", "category": "physics_bio-ph" }, { "text": "First experimental tests of the Peyrard-Bishop model applied to the\n melting of very short DNAs: The melting curves of short heterogeneous DNA chains in solution are\ncalculated on the basis of statistical thermodynamics and compared to\nexperiments. The computation of the partition function is based on the\nPeyrard-Bishop hamiltonian, which has already been adopted in the theoretical\ndescription of the melting of long DNA chains. In the case of short chains it\nis necessary to consider not only the breaking of the hydrogen bonds between\nsingle base pairs, but also the complete dissociation of the two strands\nforming the double helix.", "category": "physics_bio-ph" }, { "text": "Modeling oscillatory Microtubule--Polymerization: Polymerization of microtubules is ubiquitous in biological cells and under\ncertain conditions it becomes oscillatory in time. Here simple reaction models\nare analyzed that capture such oscillations as well as the length distribution\nof microtubules. We assume reaction conditions that are stationary over many\noscillation periods, and it is a Hopf bifurcation that leads to a persistent\noscillatory microtubule polymerization in these models. Analytical expressions\nare derived for the threshold of the bifurcation and the oscillation frequency\nin terms of reaction rates as well as typical trends of their parameter\ndependence are presented. Both, a catastrophe rate that depends on the density\nof {\\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay\nreaction, such as the depolymerization of shrinking microtubules or the decay\nof oligomers, support oscillations. For a tubulin dimer concentration below the\nthreshold oscillatory microtubule polymerization occurs transiently on the\nroute to a stationary state, as shown by numerical solutions of the model\nequations. Close to threshold a so--called amplitude equation is derived and it\nis shown that the bifurcation to microtubule oscillations is supercritical.", "category": "physics_bio-ph" }, { "text": "Detection of Anticipatory Dynamics Between a Pair of Zebrafish: Trajectories from a pair of interacting zebrafish are used to test for the\nexistence of anticipatory dynamics in natural systems. Anticipatory dynamics\n(AD) is unusual in that causal events are not necessarily ordered by their\ntemporal order. However, their causal order can still be established if the\ndirection of information flow (DIF) is known. In order to obtain DIF between\ntrajectories of the two fish, we have made use of the difference of the\ntransfer entropy between the trajectories with a history length established by\nexperiments with known DIF. Our experimental results indicate that AD can be\nobserved much more often in fish pairs of different genders. The use of DIF to\ndetermine causal order is further verified by the simulation of two chaotic\nLorenz oscillators with anticipatory coupling; mimicking the interaction\nbetween the fish. Our simulation results further suggest that the two fish are\ninteracting with their own internal dynamics, not by adaptation.", "category": "physics_bio-ph" }, { "text": "Entropic formulation for the protein folding process: hydrophobic\n stability correlates with folding rates: We assume that the protein folding process follows two autonomous steps: the\nconformational search for the native, mainly ruled by the hydrophobic effect;\nand, the final adjustment stage, which eventually gives stability to the\nnative. Our main tool of investigation is a 3D lattice model provided with a\nten-letter alphabet, the stereochemical model. This model was conceived for\nMonte Carlo (MC) simulations when one keeps in mind the kinetic behavior of\nprotein-like chains in solution. In order to characterize the folding\ncharacteristic time ({\\tau}) by two distinct sampling methods, first we present\ntwo sets of 10^{3} MC simulations for a fast protein-like sequence. For these\nsets of folding times, {\\tau} and {\\tau}_{q} were obtained with the application\nof the standard Metropolis algorithm (MA), and a modified algorithm (M_{q}A).\nThe results for {\\tau}_{q}reveal two things: i) the hydrophobic chain-solvent\ninteractions plus a set of inter-residues steric constraints are enough to\nemulate the first stage of the process: for each one of the 10^{3} MC performed\nsimulations, the native is always found without exception, ii) the ratio\n{\\tau}_{q}/{\\tau}~1/3 suggests that the effect of local thermal fluctuations,\nencompassed by the Tsallis weight, provides an innate efficiency to the chain\nescapes from energetic and steric traps. ...", "category": "physics_bio-ph" }, { "text": "Folding and unfolding of a triple-branch DNA molecule with four\n conformational states: Single-molecule experiments provide new insights into biological processes\nhitherto not accessible by measurements performed on bulk systems. We report on\na study of the kinetics of a triple-branch DNA molecule with four\nconformational states by pulling experiments with optical tweezers and\ntheoretical modelling. Three distinct force rips associated with different\ntransitions between the conformational states are observed in the folding and\nunfolding trajectories. By applying transition rate theory to a free energy\nmodel of the molecule, probability distributions for the first rupture forces\nof the different transitions are calculated. Good agreement of the theoretical\npredictions with the experimental findings is achieved. Furthermore, due to our\nspecific design of the molecule, we found a useful method to identify\npermanently frayed molecules by estimating the number of opened basepairs from\nthe measured force jump values.", "category": "physics_bio-ph" }, { "text": "Statistical Geometry of Packing Defects of Lattice Chain Polymer from\n Enumeration and Sequential Monte Carlo Method: Voids exist in proteins as packing defects and are often associated with\nprotein functions. We study the statistical geometry of voids in\ntwo-dimensional lattice chain polymers. We define voids as topological features\nand develop a simple algorithm for their detection. For short chains, void\ngeometry is examined by enumerating all conformations. For long chains, the\nspace of void geometry is explored using sequential Monte Carlo importance\nsampling and resampling techniques. We characterize the relationship of\ngeometric properties of voids with chain length, including probability of void\nformation, expected number of voids, void size, and wall size of voids. We\nformalize the concept of packing density for lattice polymers, and further\nstudy the relationship between packing density and compactness, two parameters\nfrequently used to describe protein packing. We find that both fully extended\nand maximally compact polymers have the highest packing density, but polymers\nwith intermediate compactness have low packing density. To study the\nconformational entropic effects of void formation, we characterize the\nconformation reduction factor of void formation and found that there are strong\nend-effect. Voids are more likely to form at the chain end. The critical\nexponent of end-effect is twice as large as that of self-contacting loop\nformation when existence of voids is not required. We also briefly discuss the\nsequential Monte Carlo sampling and resampling techniques used in this study.", "category": "physics_bio-ph" }, { "text": "Energy consumption and cooperation for optimal sensing: The reliable detection of environmental molecules in the presence of noise is\nan important cellular function, yet the underlying computational mechanisms are\nnot well understood. We introduce a model of two interacting sensors which\nallows for the principled exploration of signal statistics, cooperation\nstrategies and the role of energy consumption in optimal sensing, quantified\nthrough the mutual information between the signal and the sensors. Here we\nreport that in general the optimal sensing strategy depends both on the noise\nlevel and the statistics of the signals. For joint, correlated signals, energy\nconsuming (nonequilibrium), asymmetric couplings result in maximum information\ngain in the low-noise, high-signal-correlation limit. Surprisingly we also find\nthat energy consumption is not always required for optimal sensing. We\ngeneralise our model to incorporate time integration of the sensor state by a\npopulation of readout molecules, and demonstrate that sensor interaction and\nenergy consumption remain important for optimal sensing.", "category": "physics_bio-ph" }, { "text": "Initiation and blocking of the action potential in the axon in weak\n ultrasonic or microwave fields: In this paper, we analyze the effect of the redistribution of the\ntransmembrane ion channels in the axon caused by longitudinal acoustic\nvibrations of the membrane. These oscillations can be excited by an external\nsource of ultrasound and weak microwave radiation interacting with the charges\nsitting on the surface of the lipid membrane. It is shown, using the\nHodgkin-Huxley model of the axon, that the density redistribution of\ntransmembrane sodium channels may reduce the threshold of the action potential,\nup to its spontaneous initiation. At the significant redistribution of sodium\nchannels in membrane, the rarefaction zones of the transmembrane channels\ndensity are formed, blocking the propagation of the action potential. Blocking\nthe action potential propagation along the axon is shown to cause anestesia in\nthe example case of a squid axon. Various approaches to experimental\nobservation of the effects considered in this paper are discussed.", "category": "physics_bio-ph" }, { "text": "Universal Organization of Resting Brain Activity at the Thermodynamic\n Critical Point: Thermodynamic criticality describes emergent phenomena in a wide variety of\ncomplex systems. In the mammalian brain, the complex dynamics that\nspontaneously emerge from neuronal interactions have been characterized as\nneuronal avalanches, a form of critical branching dynamics. Here, we show that\nneuronal avalanches also reflect that the brain dynamics are organized close to\na thermodynamic critical point. We recorded spontaneous cortical activity in\nmonkeys and humans at rest using high-density intracranial microelectrode\narrays and magnetoencephalography, respectively. By numerically changing a\ncontrol parameter equivalent to thermodynamic temperature, we observed typical\ncritical behavior in cortical activities near the actual physiological\ncondition, including the phase transition of an order parameter, as well as the\ndivergence of susceptibility and specific heat. Finite-size scaling of these\nquantities allowed us to derive robust critical exponents highly consistent\nacross monkey and humans that uncover a distinct, yet universal organization of\nbrain dynamics.", "category": "physics_bio-ph" }, { "text": "Computational Studies of the Structural Stability of Rabbit Prion\n Protein Compared to Human and Mouse Prion Proteins: Prion diseases are invariably fatal and highly infectious neurodegenerative\ndiseases affecting humans and animals. The neurodegenerative diseases such as\nCreutzfeldt-Jakob disease, variant Creutzfeldt-Jakob diseases,\nGerstmann-Str$\\ddot{a}$ussler-Scheinker syndrome, Fatal Familial Insomnia, Kuru\nin humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow'\ndisease) and chronic wasting disease in cattle belong to prion diseases. By now\nthere have not been some effective therapeutic approaches to treat all these\nprion diseases. Dogs, rabbits and horses were reported to be resistant to prion\ndiseases. By the end of year 2010 all the NMR structures of dog, rabbit and\nhorse prion proteins (X-ray for rabbits too) had been finished to release into\nprotein data bank. Thus, at this moment it is very worth studying the NMR and\nX-ray molecular structures of horse, dog and rabbit prion proteins to obtain\ninsights into their immunity prion diseases.\n The author found that dog and horse prion proteins have stable molecular\ndynamical structures whether under neutral or low pH environments, but rabbit\nprion protein has stable molecular dynamical structures only under neutral pH\nenvironment. Under low pH environment, the stable $\\alpha$-helical molecular\nstructures of rabbit prion protein collapse into $\\beta$-sheet structures. This\narticle focuses the studies on rabbit prion protein (within its C-terminal NMR,\nHomology and X-ray molecular structured region RaPrP$^\\text{C}$ (120-230)),\ncompared with human and mouse prion proteins (HuPrP$^\\text{C}$ (125-228) and\nMoPrP$^\\text{C}$ (124-226) respectively). The author finds that some salt\nbridges contribute to the structural stability of rabbit prion protein under\nneutral pH environment.", "category": "physics_bio-ph" }, { "text": "Normal epithelial and triple-negative breast cancer cells show the same\n invasion potential in rigid spatial confinement: The extra-cellular microenvironment has a fundamental role in tumor growth\nand progression, strongly affecting the migration strategies adopted by single\ncancer cells during metastatic invasion. In this study, we use a novel\nmicrofluidic device to investigate the ability of mesenchymal and epithelial\nbreast tumor cells to fluidize and migrate through narrowing microstructures\nupon chemoattractant stimulation. We compare the migration behavior of two\nmesenchymal breast cancer cell lines and one epithelial cell line, and find\nthat the epithelial cells are able to migrate through the narrowest\nmicroconstrictions as the more invasive mesenchymal cells. In addition, we\ndemonstrate that migration of epithelial cells through a highly compressive\nenvironment can occur in absence of a chemoattractive stimulus, thus evidencing\nthat they are just as prone to react to mechanical cues as invasive cells.", "category": "physics_bio-ph" }, { "text": "Coupled dynamics of voltage and calcium in paced cardiac cells: We investigate numerically and analytically the coupled dynamics of\ntransmembrane voltage and intracellular calcium cycling in paced cardiac cells\nusing a detailed physiological model and its reduction to a three-dimensional\ndiscrete map. The results provide a theoretical framework to interpret various\nexperimentally observed modes of instability ranging from electromechanically\nconcordant and discordant alternans to quasiperiodic oscillations of voltage\nand calcium.", "category": "physics_bio-ph" }, { "text": "Hyperspectral Absorption Microscopy Using Photoacoustic Remote Sensing: An improved method of remote optical absorption spectroscopy and\nhyperspectral optical absorption imaging is described which takes advantage of\nthe photoacoustic remote sensing detection architecture. A wide range of\nphotoacoustic excitation wavelengths ranging from 210 nm to 1550 nm was\nprovided by a nanosecond tunable source allowing access to various salient\nendogenous chromophores such as DNA, hemeproteins, and lipids. Sensitivity of\nthe device was demonstrated by characterizing the infrared absorption spectrum\nof water. Meanwhile, the efficacy of the technique was explored by recovering\ncell nuclei and oxygen saturation from a live chicken embryo model and by\nrecovering adipocytes from freshly resected murine adipose tissue. This\nrepresents a continued investigation into the characteristics of the\nhyperspectral photoacoustic remote sensing technique which may represent an\neffective means of non-destructive endogenous contrast characterization and\nvisualization.", "category": "physics_bio-ph" }, { "text": "A zero-depth nanopore capillary for the analysis of translocating\n biomolecules: High-fidelity analysis of translocating biomolecules through nanopores\ndemands shortening the nanocapillary length to a minimal value. Existing\nnanopores and capillaries, however, inherit a finite length from the parent\nmembranes. Here, we form nanocapillaries of zero depth by dissolving two\nsuperimposed and crossing metallic nanorods, thereby opening two overlapping\nnanofluidic channels molded in a polymeric resin. In an electrolyte, the\ninterface shared by the crossing fluidic channels is mathematically of zero\nthickness and defines the narrowest constriction in the stream of ions through\nthe nanopore device. This novel architecture provides the possibility to design\nnanopore fluidic channels, particularly with a robust 3D architecture\nmaintaining the ultimate zero thickness geometry independently of the thickness\nof the fluidic channels. With orders of magnitude reduced biomolecule\ntranslocation speed, and lowered electronic and ionic noise compared to\nnanopores in 2D materials, our findings establish interfacial nanopores as a\nscalable platform for realizing nanofluidic systems, capable of single-molecule\ndetection.", "category": "physics_bio-ph" }, { "text": "A Diffusion-Based Approach to Geminate Recombination of Heme Proteins\n with Small Ligands: A model of postphotodissociative monomolecular (geminate) recombination of\nheme proteins with small ligands (NO, O2 or CO) is represented. The\nnon-exponential decay with time for the probability to find a heme in unbound\nstate is interpreted in terms of diffusion-like migration of ligabs\nphysics/0212040 and between protein cavities. The temporal behavior for the\nprobability is obtained from numerical simulation and specified by two\nparameters: the time \\tau_{reb} of heme-ligand rebinding for the ligand\nlocalized inside the heme pocket and the time \\tau_{esc} of ligand escape from\nthe pocket. The model is applied in the analysis of available experimental data\nfor geminate reoxygenation of human hemoglobin HbA. Our simulation is in good\nagreement with the measurements. The analysis shows that the variation in pH of\nthe solution (6.0