February 2017
EPL, 117 (2017) 38001
doi: 10.1209/0295-5075/117/38001

www.epljournal.org

Localization and diffusion of tracer particles in viscoelastic media
with active force dipoles
Kento Yasuda1 , Ryuichi Okamoto1 , Shigeyuki Komura1 and Alexander S. Mikhailov2,31

Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University
Tokyo 192-0397, Japan2
Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society - Faradayweg 4-6,14195 Berlin, Germany
3
Department of Mathematical and Life Sciences, Hiroshima University - Hiroshima 739-8526, Japan
received 24 December 2016; accepted in final form 21 February 2017
published online 15 March 201787.16.dj – Dynamics and ﬂuctuations
87.16.Uv – Active transport processes
PACS 83.60.Bc – Linear viscoelasticity
PACS
PACS

Abstract – Optical tracking in vivo experiments reveal that diﬀusion of particles in biologicalcells is strongly enhanced in the presence of ATP and the experimental data for animal cells
could previously be reproduced within a phenomenological model of a gel with myosin motors
acting within it (Fodor É. et al., EPL, 110 (2015) 48005). Here, the two-ﬂuid model of a gel
is considered where active macromolecules, described as force dipoles, cyclically operate both in
the elastic and the ﬂuid components. Through coarse-graining, eﬀective equations of motions
for idealized tracer particles displaying local deformations and local ﬂuid ﬂows are derived. The
equation for deformation tracers coincides with the earlier phenomenological model and thus
conﬁrms it. For ﬂow tracers, diﬀusion enhancement caused by active force dipoles in the ﬂuid
component, and thus due to metabolic activity, is found. The latter eﬀect may explain why ATPdependent diﬀusion enhancement could also be observed in bacteria that lack molecular motors intheir skeleton or when the activity of myosin motors was chemically inhibited in eukaryotic cells.
c EPLA, 2017
Copyright Introduction. – High-precision optical tracking experiments demonstrate that diffusion of microinjected
or natural particles is strongly enhanced in the presence of ATP and, generally, under metabolic activity inthe cytoplasm of a biological cell [1,2]. Similar behavior was previously found for diffusion within the nucleoplasm [3,4]. Thus, non-thermal active noises apparently
dominate transport processes inside living cells. Two possible explanations have been proposed. The first of them
relates the observed effects to activity of myosin motorsthat cross-link actin polymer filaments in eukaryotic (animal) cells [5,6]. Importantly, strong diffusion enhancement in the presence of ATP could also be observed invitro in the experiments with synthetic actin-myosin systems [7]. Another possibility is that non-thermal noise is of
metabolic origin and it arises from fluid agitation causedby active conformational changes in protein molecules
within the cytoplasm [1,8]. Such explanation is supported
by experimental results for bacteria (i.e., prokaryotic microorganisms) that lack molecular motors in their skeleton

but where strong diffusion enhancement is nonethelessobserved [1] (and ATP-dependent diffusion enhancement
was also found when the skeleton had been dissolved [1]).
Recently, it was moreover demonstrated that both the
tracking and the microrheology data on active diffusion
in eukaryotic cells can be reproduced in the framework ofa phenomenological model for the motion of tracer particles trapped inside an elastic environment and subject
only to active forces generated within it [9].
In this letter, the problem is analyzed within a general model of a viscoelastic medium that combines strain
fluctuations caused by molecular motors in the gel andmechanical agitation of the fluid component caused bymetabolic activity within it. The classical two-fluid description is employed for the viscoelastic medium [10] andmolecular motors, enzymes and other protein machines aremodeled as active force dipoles. We introduce two kinds ofhypothetical non-invasive tracers that are intended to visualize, respectively, elastic deformations and fluid flows.
Reduced equations for random motion of both kinds of38001-p1

Kento Yasuda et al.
particles are derived. As we find, the derived equation
for deformation tracers coincides with the previously proposed phenomenological model [9]. On the other hand,relative random motion of flow tracers with respect tothe elastic component is described by a Langevin equation
with non-thermal metabolic noise.
Our analysis reveals that localization and diffusion phenomena are generally involved. The motion of tracers immobilized within the elastic subsystem is localized in thelong-time limit, but it can show a diffusion-like behavior
at the intermediate time scales shorter than the cooperative correlation times of molecular motor aggregates (i.e.,
myosin microfilaments) operating in the active gels of eukaryotes, as also found in the phenomenological model [9].
On the other hand, motion of flow tracers remains diffusive in the long-time limit, and such active diffusion iscontrolled by metabolic processes that take place both inprokaryotes and eukaryotes. Assuming that the motion ofreal tracer particles represents repeated attachment anddetachment to the polymer network, we expect for it a
combination of localization and diffusion effects.

the local dynamics of the gel because, for instance, theassumption of the small volume fraction of the non-fluid
component will not be satisfied at the location of such aparticle.
To avoid these complications, motions of non-invasive
flow velocity and deformation tracers will be consideredby us. A flow velocity tracer can be introduced by choosing a certain volume element of the fluid and following
its motion with time. Similarly, a deformation tracer represents a chosen volume element of the elastic component. The tracers can only follow those velocity and deformation fluctuations whose characteristic length scaleis larger than the tracer size a. Hence, they visualize
the coarse-grained fluctuating fields obtained by averaging over the volume elements of linear size a. Such fields
include only the contributions from spatial Fourier modes
with wave numbers smaller than qc = 4π/a. The coarsegrained velocity anddeformation fields are defined asVα (r, t) = (2π)−3 |q|<qc dq vα (q, t)e−iq·r and Uα (r, t) =(2π)−3 |q|<qc dq uα (q, t) e−iq·r , respectively.

Generally, both compression and shear deformations
will be induced. We shall however only consider shear
deformations because they can be visualized by incompressible tracers. Retaining only such deformations andperforming a transformation to the spatial Fourier components of involved fields, we obtain from eqs. (1) and (2)∂uα (q, t)2
0 = −μq uα (q, t) − Γ− vα (q, t)∂t+ (δαβ − q̂α q̂β )fβu (q, t),(3)∂uα (q, t)
0 = −ηq 2 vα (q, t) − Γ vα (q, t) −∂t
If the volume fraction of the elastic component is small,(4)+ (δαβ − q̂α q̂β )fβv (q, t),
the conservation equation ∇ · v = 0 should additionallyhold. Here, μ and λ are the Lamé coefficients of the elastic where the last terms represent transverse components of
network, η is the fluid viscosity, and p is the pressure field the fluctuating force fields and we have introduced the nothat can be eliminated by using the above incompress- tations q̂α = qα /|q| = qα /q. Summation over the repeatedibility condition. The coefficient Γ specifies the relative indices will be assumed throughout this letter.
The forces are generated by active elements, attachedstrength of viscous friction forces when an elastic networkis dragged by the fluid that flows through it. The approx- to the elastic network or suspended in the fluid. Beimate continuum description for a polymer gel holds only cause they are caused by internal dynamics within suchon the length scales that are much larger than the mesh elements, the net total force generated by each element
size which is usually close in its magnitude to the char- vanishes. However, the elements still can act as force
1/2
acteristic length ℓ = (η/Γ) . Moreover, a characteristic dipoles. A force dipole i is characterized by a unit vecviscoelastic relaxation time τ = η/μ can be also defined. tor êi of its orientation and by its magnitude mi (for a
Equations (1) and (2) include forces f u and f v that are ap- force dipole formed by a pair of forces Fi and −Fi at theplied, respectively, to the elastic and the fluid components. points separated by distance di , we have mi = Fi di ). It
Since we are only interested in non-thermal fluctuations, can also be described by a nematic tensor with the elements Ni,αβ = mi (êi,α êi,β − δαβ /3) [4]. Note that this
we do not include into such forces the thermal noise.
nematic
tensor is invariant with respect to the inversion
To study diffusion in viscoelastic biological systems,
→
−ê
ê
i
i and hence the direction of the vector êi for a
tracer particles with diameters a significantly larger than
given
line
orientation can be arbitrarily assigned. Below
the mesh size are employed (a ≫ ℓ). The dynamics of
we
use,
for
convenience, the tensor Mi with the elements
such particles inside a gel is itself a complicated problem;
M
=
m
i,αβ
i êi,α êi,β .
it depends on the mechanical properties of such particlesu(v)We assume that the orientations êiand positions
and on their interactions with the polymer network [11].
u(v)of force dipoles are fixed in time, but are randomly
Moreover, the presence of big particles will also modify ri
The model. – Our study is based on the two-fluid
model of gels [10]. A viscoelastic medium is describedby the distributions of elastic deformations u(r, t) andfluid velocities v(r, t) within it. Neglecting inertial effects
that do not play a role on the considered time scales, theevolution of the two fields is governed by∂u− v + f u , (1)0 = μ∇2 u + (μ + λ) ∇ (∇ · u) − Γ
∂t


∂u
(2)
0 = η∇2 v − ∇p − Γ v −+ f v.
∂t

38001-p2

Localization and diffusion of tracer particles in viscoelastic media
distributed. Spatial distributions of the two kinds of active force dipoles are given by fluctuating tensor fields
defined as u(v)u(v) u(v)u(v)u(v)
mi (t)êi,α êi,β δ(r − ri ),(5)Mαβ (r, t) =|q| < qc . The simplifying assumption is that the tracer
is big, namely, that its diameter is much larger than themesh size or, explicitly, that the condition qc ℓ ≪ 1 is satisfied (note that qc ∼ 1/a).
Green functions g of the two-fluid model in eqs. (1)iand (2) have been derived by Levine and Lubensky[12,13]. They allow us to express deformation and veu(v)which satisfies Mαβ  = 0. A single active force dipole locity fields in terms of the applied forces, i.e., to write
is characterized by the correlation function S u(v) (t) = uα (q, ω) = g uu (q, ω)f u (q, ω) + g uv (q, ω)f v (q, ω) and
αβ
β
αβ
β
vu
vv
mu(v) (t)mu(v) (0) (see later eq. (28)).
(q, ω)fβu (q, ω) + gαβ(q, ω)fβv (q, ω). Usingvα (q, ω) = gαβ
The dipoles are statistically independent and correlation these Green functions which express the forces in terms offunctions for their tensor fields are
the force dipoles through eq. (10), and performing algebraic transformations, we obtain the following expressions
u(v)
u(v)
Mαβ (r, t) Mα′ β ′ (0, 0) =for transverse components of the deformation and velocity
fields:cu(v)(δαβ δα′ β ′ + δαα′ δββ ′ + δαβ ′ δβα′ ) δ(r)S u(v) (t), (6)
15
u
uv
v
uα (q, ω) = Guu
αβγ Mβγ (q, ω) + Gαβγ Mβγ (q, ω), (11)
u
v
u
vv
v
where c and c are the concentrations of force dipoles.
vα (q, ω) = Gvu
αβγ Mβγ (q, ω) + Gαβγ Mβγ (q, ω), (12)We also assume that cross-correlations are absent,uMαv′ β ′  = 0, although they can easily be included, with Gαβγ (q, ω) = igαβ (q, ω)qγ or, explicitly,
Mαβ
too.
1 + q 2 ℓ2
The active force fields f can be expressed in terms of theQαβγ (q̂),
(13)
Guu
αβγ =
μq(1 + q 2 ℓ2 + iωτ )tensor fields M of the dipoles. Assuming that each force
1
dipole i corresponds to a pair of forces Fi and −Fi whoseQαβγ (q̂),
Guv
(14)
αβγ =
2
μq(1 + q ℓ2 + iωτ )application points are separated by a vector di êi , we haveiωτ
Qαβγ (q̂),
Gvu
(15)
αβγ =
fα (r, t) =Fi (t)êi,α [δ(r − ri − di êi ) − δ(r − ri )] , (7)ηq(1 + q 2 ℓ2 + iωτ )iiωτ + q 2 l2Qαβγ (q̂),
(16)
Gvv
αβγ =
and thereforeηq(1 + q 2 ℓ2 + iωτ )where we have introduced Qαβγ (q̂) = i (δαβ − q̂α q̂β ) q̂γ .
fα (q, t) = dr fα (r, t)eiq·r =The above results can be simplified if only the modes
withsmall wave numbers qℓ ≪ 1 are considered (but q 2 ℓ2
Fi (t)êi,α [exp(iq · ri + idi q · êi ) − exp(iq · ri )] , (8)may still be larger than ωτ ). By performing the inversei
Fourier transform to the time-dependent deformation amwhere we have dropped the superscripts u or v. Consider- plitude u(q, t) and the velocity amplitude v(q, t), reduced
ing the modes with the wavelengths that are much larger evolution equations for these variables can be derived.
than the distances between the forces, i.e., qdi ≪ 1, we
For the deformation field, we thus findapproximately obtain∂uα (q, t)= −μuα (q, t)η∂tfα (q, t) = i
Fi (t)di qβ êi,α êi,β exp(iq · ri ),(9)Qαβγ (q̂) uiv[Mβγ (q, t) + Mβγ+(q, t)]. (17)q
and thusu(v)(10) On the other hand, the velocity field can be generally writfαu(v) (q, t) = iqβ Mαβ (q, t).
ten as
Notice that, although we have derived this equation for∂u(q, t)pairs of forces, it is more general. On the length scales+ w(q, t),(18)v(q, t) =∂tmuch longer than its own size, each object that asymmetrically changes its shape can be described as some force separating the contribution w that represents the relative
dipole. Taken together, eqs. (3) and (4) with the above fluid velocity in the co-moving coordinate frame associatedexpressions for the forces provide a complete description with the elastic component. For such relative velocity, theof the viscoelastic system with active force dipoles.
evolution equation becomes
Motion of tracer particles. – Reduced equations∂wα (q, t)
μℓ2v= −μwα (q, t)+qQαβγ (q̂)Mβγ(q, t). (19)that describe stochastic motion of tracers can be derived. η∂tηThis motion is characterized by coarse-grained deformation and velocity fields that include only spatial Fourier Notice here that, whereas any force dipoles present in thecomponents with relatively small wave vectors, such that medium will have an effect on the deformations in the38001-p3

Kento Yasuda et al.
elastic component in eq. (17), only the force dipoles acting
on the fluid component of the medium will be affecting therelative velocity w in eq. (19).
Equation (17) can be used to obtain an effective equation of motion for the deformation tracer immobilized in
the elastic component. The spatial position U(t) of sucha tracer with respect to an arbitrary reference point (thatcan be conveniently chosen as the origin of coordinatesr = 0) is given by Uα (t) = (2π)−3 |q|<qc dq uα (q, t). Withthe use of eq. (17), the stochastic Langevin equation forthe deformation tracer is finally obtained as

fluid component. Thus, we have derived effective eqs. (20)and (24) for the motion of the two kinds of tracers thatvisualize, respectively, polymer network deformations andflows in the fluid component.
We note here that eq. (20) coincides with the phenomenological model used by Fodor et al. [9]. In theirmodel, the spatial position x of a tracer particle immobilized in the network was assumed to follow the stochastic
equationdx= −kx + fA (t),
(27)
γ
dt
if we omit the thermal random forces. In the above, γdUα= −μUα + Fαu (t),(20) was the friction coefficient of the environment, k was theηdtspring constant of the surrounding network, and fA (t) was
where the time-dependent random force Fu (t) is defined as the fluctuating active force. To fit the model predictions to
the experimental results, it was necessary to assume that γ
dq Qαβγ (q̂) u
and k were both proportional to the tracer size a, and thatuv
Fα (t) =[Mβγ (q, t) + Mβγ (q, t)].
3
themagnitude of the active force scaled as fA ∼ a1/2 [9].
(2π)
q|q|<qc(21) The model described by eq. (27) is straightforwardly obtained from eq. (20) if we identify the tracer position x as
1/2
U, and introduce γ = η/qc , k = μ/qc and fA = Fu /qc ,The correlation function of this random force iswhere qc ∼ 1/a as before. According to eq. (21), the active
Fαu (t)Fβu (0) = ζ u qc [cu S u (t) + cv S v (t)]δαβ ≡ H u (t)δαβ ,force fA should actually have contributions coming both(22) from the force dipoles in the elastic and fluid componentsof the medium.
where the coefficient can be calculated as ζ u = 1/(45π 2 )Localization vs. diﬀusion. – Using eqs. (20)due to the following integral over all orientations of theand(24), one can determine time dependences of theunit vector q̂:mean-square displacements (MSD) for both kinds of trac
ers. The analysis is simplified if we take into account that,
8π
δαβ .
(23)
dq̂ Qαγδ (q̂)Qβγδ (−q̂) =for biological cells, the viscoelastic relaxation time τ can3
be estimated as being about 1 ms, and this is much shorter
In a similar manner, a stochastic equation of motion than the typical times over which particle positions canfor fluid velocity tracers can be obtained. According to be experimentally traced. Moreover, it would be typicallyeq. (18), the tracer velocity can be split into two parts, also shorter than correlation times of active force dipoles.
V = dU/dt + W. The first part represents the velocity of On the time scales much longer than τ , the time derivativea tracer if it were immobilized in the elastic component. terms in eqs. (20) and (24) can be dropped and they reduce
This contribution to the tracer velocity can be determined to Uα (t) = F u (t)/μ and Wα (t) = F w (t)/μ, respectively.
ααby using eq. (20). In contrast to this, the second con- Hence, the local position of the deformation tracer andtribution yields the relative instantaneous velocity of the the local relative velocity of the flow tracer follow instanconsidered tracer with respect to the elastic component, taneously the applied forces. Therefore, statistical propsuch as the polymer network. By using eq. (19), we find erties of such active forces should play an important role.
a stochastic Langevin equation for it as
Various kinds of active macromolecules in a biologicalcell
can contribute to the force dipole activity within it.
dWα= −μWα + Fαw (t),(24) Active force dipoles operating in the fluid subsystem areηdtof metabolic origin. They correspond to enzymes that
undergo repeated conformational changes and thus stirwhere the random force is defined asmechanically the cytoplasm. In contrast to this, force

dq
μℓ2
v
dipoles operating in the elastic subsystem are associatedFαw (t) =
qQ
(q̂)M
(q,
t).
(25)
αβγ
βγ
η |q|<qc (2π)3with molecular motors such as myosin, kinesin and dynein.
Because of their activity, the skeleton of eukaryotic cells
Then its correlation function can be calculated as
represents an active gel. In bacteria and other prokary2 5 4otes, however, molecular motors are absent. Hence, theirℓμqcFαw (t)Fβw (0) = ζ w
cv S v (t)δαβ ,(26) gel is passive and only the forces of metabolic origin are
η2
in operation in them.
where ζ w = 1/(225π 2 ) (see also eq. (23)). This random
Different kinds of active macromolecules in the cell will
force is determined only by the force dipoles acting on the have different correlation functions of their force dipoles,
38001-p4

Localization and diffusion of tracer particles in viscoelastic media
and such macromolecules will be present in different concentrations. While we have assumed for simplicity that
only one group of elastic force dipoles and one group of
fluid force dipoles are present with their concentrations
cu and cv , respectively, summation over different kindsof macromolecules within each group has actually to be
performed. Because of this, no universal expressions for
dipole correlation functions can be formulated. For simple estimates, we can however assume that, within eachgroup, dipoles are exponentially correlated in time withsome correlation times τ u and τ v and we haveS u(v)|t|
S u(v) (t) = u(v) exp − u(v) ,
(28)
2τ
τ

fA satisfied the equation dfA /dt = νA where νA (t) represented an active delta-correlated noise.
Next, we consider the motion of flow tracers in the fluid
component. Their time-dependent position vector isRα (t) = Uα (t) + t

dt1 Wα (t1 ),

(33)

0

with the relative flow velocity W satisfying eq. (24). By
using this definition, the MSD for flow tracers can be obtained as2∆Rα(t) = ∆Uα2 (t)
 t
 t
1
+ 2
dt2 Fαw (t1 − t2 ) Fαw (0). (34)
dt1
μ 0
0

where S u and S v are integral intensities of the respective
force dipoles.
In the long-time limit with t ≫ τ u and t ≫ τ v , we find
The MSD for deformation tracers is obtained fromeq. (22) asR2 (t) = U 2 ∞ + 6Dv t,
(35)
α

2
[H u (0) − H u (t)],μ2(29)
where H u (t) is the correlation function of the elastic active
forces introduced in eq. (22). In the long-time limit, or attimes t much longer than the correlation times τ u and τ vof all active force dipoles, we have H u (t) → 0. Hence,
the MSD remains finite in this limit and localization isobserved. The localization radius is then determined by
the square root of
 u u

c S
qc
cv S v+
Uα2 ∞ =,(30)
15π 2 μ2τuτv
2∆Uα2 (t) = (Uα (t) − Uα (0))  =and it decreases with the particle size as a−1/2 .
In active gels of eukaryotes, myosin motors that crosslink actin filaments are operating in large aggregates(microfilaments) [7]. Each microfilament gives rise to aneffective elastic force dipole and correlation times τ u forthe cooperative activity of such motor groups can be long(about several seconds). Myosin microfilaments give rise
to a time-dependent contribution into the deformation
MSD at intermediate times, τ v ≪ t ≪ τ u . For suchcontribution, one finds that
qc cu S ut2∆Uα (t) =1 − exp − u≈ 6Du t, (31)
15π 2 μ2 τ u
τ
where
Du =

qc cu S u.
90π 2 (μτ u )2(32)

Hence, within this time range, deformation tracers will
perform an apparent diffusive motion with the “diffusion”
coefficient Du . Note that such a diffusion coefficient isinversely proportional to the particle size a, like the size
dependence of the equilibrium diffusion coefficient givenby the Stokes-Einstein relation. The above result could
previously be obtained [9] in the framework of the phenomenological eq. (27) by assuming that the active force

αwhere the diffusion coefficient is given byDv =qc5 ℓ4 cv S v.
450π 2 η 2(36)Hence, the asymptotic MSD for flow tracers will include
both the localization and diffusion parts. The diffusion is
weak, but it would nonetheless dominate over the localization at sufficiently long times, i.e., for t ≫ τ 2 /(τ v qc4 ℓ4 ).
Finally, the behavior of real physical tracers can be discussed. Our conjecture is that a big tracer would stochastically alternate between the two states, i.e., when it isbound to the elastic component or is free to move withthe fluid component. Under such assumption, its observed
MSD ∆Xα2 (t) will be a superposition of the MSDs of deformation and fluid velocity tracers,2∆Xα2 (t) = κ∆Rα(t) + (1 − κ)∆Uα2 (t),(37)

with some weight coefficient 0 ≤ κ ≤ 1. Therefore, in thelimit t → ∞, we would have∆Xα2 (t) = Uα2 ∞ + 6κDv t.

(38)

Thus, the asymptotic motion of the tracers will represent
a combination of spatial localization and of the diffusion
process.
Discussion. – The relationship between our theoretical results and the experimental data [1,2,9] can be
discussed. Under physiological conditions in eukaryotic
cells, cooperative activity of myosin motors assembled
into microfilaments acting onto the polymer network suffices to explain the main experimental results, as has
been previously pointed out [2,9]. The experimentally observed regime corresponds to the intermediate diffusionlike asymptotic behavior (see eq. (31)) which originatesfrom very long correlations times of the force dipoles that
correspond to myosin microfilaments.

38001-p5

Kento Yasuda et al.
In the experiments [2,9], it was moreover possible tochemically inhibit myosin activity while still having ATP
inside a cell. Additionally, tracking experiments were also
performed in the same cells under depletion of ATP. It
was found that myosin inhibition reduces the diffusion
coefficient by about a factor of ten, but the remaining
diffusion was still much larger than what was observed
without ATP. Since myosin contribution has been suppressed, different mechanisms should have contributed to
the remaining ATP-dependent diffusion enhancement inthis case.
Note that, besides myosin, eukaryotes have other molecular motors such as kinesin and dynein in the cytoskeleton. However, these other motors do not form aggregates,
similar to myosin microfilaments, and therefore they cannot lead to long correlation times (of the order of several
seconds) that are needed to have the diffusion-like asymptotic behavior in eq. (31). Furthermore, strong diffusion
decrease under ATP depletion (or under starvation conditions) was also observed in optical tracking experimentswith bacteria that lack molecular motors in their skeleton [1]. Hence the mechanisms not involving molecularmotors should have been at play.
Our analysis indicates that, in viscoelastic media withactive force dipoles, not only localization, but also diffusion of tracer particles will be observed in the limit oflong times (see eq. (35)). According to eq. (36) for Dv ,such active diffusion is determined only by force dipolesin the fluid component. They should be of metabolic origin and are due to active conformational changes that accompany turnover cycles of enzymes [1,8]. Note that, in
accordance with eq. (30), both diffusion and localization
should take place.
The diffusion should prevail over the localization at
the times much longer than the crossover time t∗ ≈
τ 2 /(τ v qc4 ℓ4 ). If the size a ∼ 1/qc of a tracer is about
ten times larger than the mesh size ℓ, and the viscoelastic
time τ (typically about 1 ms) is about ten times shorter
than the correlation time τ v for metabolic force dipoles,
we find that the crossover to classical diffusion from thesaturation plateau should be after the time t∗ which isabout 1 s. This can explain why such a plateau was notseen, and only classical diffusion was found, in the experiments with bacteria where the shortest time intervals were
15 s [1]. On the other hand, a plateau of about this duration has been indeed observed in the animal cells under
inhibition of myosin motors [2].
It should be pointed out that the obtained results hold
only for relatively big tracer particles, with the sizes muchlarger than the mesh size (about 50 nm) of the intracellularpolymer network. For the tracers with the sizes smaller
than the mesh size, the previous analysis in ref. [8] willapproximately hold.
In this study, the analysis was performed assuming idealized non-invasive flow and deformations tracers thatserve only to visualize motions of fluid and elastic elements, without affecting flow and deformation fields

themselves. The idealized flow tracers are therefore “nonsticky” and roughly correspond to those considered in a
recent publication [14]. In contrast to this, deformation
tracers interact strongly with the elastic component andare bound within it. To obtain an estimate of eq. (37), we
have further assumed that the physical tracer alternates
randomly between its free and bound states. It should
be stressed that this is a simplification and the situation
for real tracers can be much more complicated (see, e.g.,ref. [11]). Interactions between a tracer and the elastic network depend on the ratio between the size of the tracers
and the mesh size of the polymer network. When experiments with big solid tracers are performed, such tracers would certainly significantly distort flows of the fluid
around them.
The classical two-fluid model of gels was introduced
about four decades ago by de Gennes [10] and muchprogress has been made afterwards [15,16], with various
detailed descriptions for the gels available today (see, e.g.,
refs. [17,18]). The present analysis is however done entirely
within the original description [10] in order to demonstrate
what should be expected in its framework. Remarkably,
we could then reproduce the phenomenological model [9]that shows good agreement with the experimental data foreukaryotic cells (see also the related publication [19]). Extensions and generalizations of our results to other models
of gels can be performed, and this will be the task of additional work.
The two-fluid model treats a gel as an elastic solid
network with the fluid flowing through it. Real gels are
however only partially solid and begin to flow at a finite
viscosity themselves on sufficiently long time scales [15].
Thus, our analysis needs to be modified at such longer
time scales. The characteristic time when the actin gel
starts to flow is of the order 100–1000 s [15]. Note that,
according to Guo et al. [2], their tweezer measurements
confirmed that the cytoplasm is an elastic solid across themeasured timescales.
Furthermore, we have not considered here the glass
behavior which arises even in the absence of the polymer network because the cytoplasm represents a crowded
colloidal suspension. Previously, such behavior was investigated at thermal equilibrium [20,21]. Experimental
data for bacterial cells shows that subdiffusion characteristic for glassy systems disappears in the presence of
metabolic activity inside a cell and that classical diffusion
is then observed [1]. Investigations of the effects of active
force dipoles on crowded colloidal suspensions may be aninteresting subject for future research.
∗∗∗
Stimulating discussions with D. Mizuno are gratefully
acknowledged. SK and RO acknowledge support from theGrant-in-Aid for Scientific Research on Innovative Areas“Fluctuation and Structure” (Grant No. 25103010) from
the Ministry of Education, Culture, Sports, Science, and

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Localization and diffusion of tracer particles in viscoelastic media
Technology of Japan, and the Grant-in-Aid for Scientific
Research (C) (Grant No. 15K05250) from the Japan Society for the Promotion of Science (JSPS). This study
was moreover supported through the EU program (Grant
No. PIRSES-GA-2011-295243 to ASM) for collaborations
with Japan.

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