ACTIVE BIO-SYSTEMS: FROM SINGLE MOTOR MOLECULES TO COOPERATIVE CARGO TRANSPORT
Authors: LIPOWSKY REINHARD , BEEG JANINA , DIMOVA RUMIANA , KLUMPP STEFAN , LIEPELT STEFFEN , MÜLLER MELANIE J. I. , VALLERIANI ANGELO 
Published: May 2009

Living cells contain a large number of molecular motors that convert the chemical energy released from nucleotide hydrolysis into mechanical work. This review focusses on stepping motors that move along cytoskeletal filaments. The behavior of these motors involves three distinct nonequilibrium processes that cover a wide range of length and time scales: (i) Directed stepping of single motors bound to a filament; (ii) Composite motor walks of single motors consisting of directed stepping interrupted by diffusive motion; and (iii) Cooperative transport by teams of several motors. On the molecular scale, the energy conversion of these motors leads to single steps along the filaments with a step size of about 10 nm. The corresponding chemomechanical coupling is governed by several distinct motor cycles, which represent the dominant pathways for different values of nucleotide concentrations and load force. For the kinesin motor, the competition of two such cycles determines the stall force, at which the motor velocity vanishes and the motor reverses the direction of its motion. Because of thermal noise, the stepping motors unbind from the filaments after a certain run time and run length. For kinesin, the run time is about 1 s and the run length is about 1 μm for high ATP concentration and low load force. On length scales that are large compared to the run length, a single motor undergoes composite walks consisting of directed stepping interrupted by diffusive motion. The relative importance of bound and unbound motor states depends on the binding and unbinding rates of the motors. The effective transport velocity and diffusion coefficient of the motors are determined by the geometry of the compartments, in which the motors move. The effective diffusion coefficient can be enhanced by several orders of magnitude if the motors undergo active diffusion by interacting with certain filament patterns. In vivo, stepping motors are responsible for the transport of vesicles and other types of intracellular cargo particles that shuttle between the different cell compartments. This cargo transport is usually performed by teams of motors. If all motors belong to the same molecular species, the cooperative action of the motors leads to uni-directional transport with a strongly increased run length and to a characteristic force dependence of the velocity distributions. If two antagonistic species of motors pull on the cargo, they perform a stochastic tug-of-war, which is characterized by a subtle force balance between the two motor teams and leads to seven distinct patterns of uni- and bi-directional transport. So far, all experimental observations on bi-directional transport are consistent with such a tug-of-war. Finally, the traffic of interacting motors is also briefly discussed. Depending on their mutual interactions and the compartment geometry, the motors form various spatio-temporal patterns such as traffic jams, and undergo nonequilibrium phase transitions between such transport patterns.