Transition to superdiffusive behavior in intracellular actin-based transport mediated by molecular motors

Abstract

Intracellular transport of large cargoes, such as organelles, vesicles or large proteins, is a complex dynamical process that involves the interplay of ATP-consuming molecular motors, cytoskeleton filaments and the viscoelastic cytoplasm. The displacements of particles or probes in the cell cytoplasm as a function of time are characterized by different (anomalous) diffusion regimes. We investigate here the motion of pigment organelles (melanosomes) driven by myosin-V motors in Xenopus laevis melanocytes using a high spatio-temporal resolution tracking technique. By analyzing the mean square displacement (MSD) of the obtained trajectories as a function of the time lag, we show that the melanosomes display a transition between subdiffusive to superdiffusive behavior. A stochastic theoretical model is introduced to generalize the interpretation of our data. Starting from a generalized Langevin equation that explicitly considers the collective action of the molecular motors we derive an analytical expression for the MSD as a function of the time lag, which also takes into account the experimental noise. By fitting our model to the experimental data we were able to discriminate the exponents that characterize the passive and active contributions to melanosome dynamics. The model also estimates the "global" motor forces correctly. In this sense, our model gives a quantitative description of active transport in living cells with a reduced number of parameters.

Scaling Green-Kubo Relation and Application to Three Aging Systems

“…(35) and (36) describe the motion of the tracer in a crowded equilibrium environment, which is known to exhibit subdiffusion with exponent ν ¼ 1 − ρ [24,25]. If ηðtÞ is considered to be an external noise driving the system out of equilibrium, the fluctuation-dissipation theorem does not hold, and the system may become superdiffusive [28,29]. In living cells, this external noise is due to the action of molecular motors and it drives active transport [28].…”

“…If ηðtÞ is considered to be an external noise driving the system out of equilibrium, the fluctuation-dissipation theorem does not hold, and the system may become superdiffusive [28,29]. In living cells, this external noise is due to the action of molecular motors and it drives active transport [28]. It requires an external source of energy (e.g., ATP) to continuously keep the system out of equilibrium [60].…”

“…In Refs. [28,29], an external nonequilibrium noise term was introduced to describe the superdiffusive behavior due to active forces in living cells. In this superdiffusive regime, we use our scaling GreenKubo relation to determine the diffusive properties from the velocity autocorrelation.…”

Superdiffusive mass transport as a causal mechanism for large-scale structure formation

“…The transport of matter within such systems can also be anomalous, such as when the mean-squared particle displacements grow faster than linearly in time. Examples of such superdiffusive systems include dusty plasmas [6,7], intracellular transport [8][9][10], turbulent fluids [11], self-propelled particles [12][13][14] and granular media [15][16][17].…”

“…-Many materials of biological or industrial importance are driven far from thermodynamic equilibrium by an imposed energy flux, mediated by e.g. motor proteins in living cells, or boundary-induced flow of fluids or particulate matter [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Given a mechanism for energy dissipation and sufficient relaxation time, such systems may reach a statistical steady state in which macroscopic quantities remain constant.…”