## How Molecular Motors Work in the Crowded Environment of Living Cells: Coexistence and Efficiency of Normal and Anomalous Transport

Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

Igor Goychuk, Vasyl O. Kharchenko, Ralf Metzler. How Molecular Motors Work in the Crowded Environment of Living Cells: Coexistence and Efficiency of Normal and Anomalous Transport, PLoS ONE 9(3): e91700 (2014)

## Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion

The discovery of anomalous diffusion of larger biopolymers and submicron tracers such as endogenous granules, organelles, or virus capsids in living cells, attributed to the viscoelastic nature of the cytoplasm, provokes the question whether this complex environment equally impacts the active intracellular transport of submicron cargos by molecular motors such as kinesins: does the passive anomalous diffusion of free cargo always imply its anomalously slow active transport by motors, the mean transport distance along microtubule growing sublinearly rather than linearly in time? Here we analyze this question within the widely used two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubules driven by a flashing binding potential, where the cargo particle is elastically attached to the motor. Depending on the cargo size, the loading force, the amplitude of the binding potential, the turnover frequency of the molecular motor enzyme, and the linker stiffness we demonstrate that the motor transport may turn out either normal or anomalous, as indeed measured experimentally. We show how a highly efficient normal active transport mediated by motors may emerge despite the passive anomalous diffusion of the cargo, and study the intricate effects of the elastic linker. Under different, well specified conditions the microtubule-based motor transport becomes anomalously slow and thus significantly less efficient.

Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion, Phys.Chem.Chem.Phys., 16, 16524 (2014)

## Anomalous Features of Diffusion in Corrugated Potentials with Spatial Correlations: Faster than Normal, and Other Surprises

Normal diffusion in corrugated potentials with spatially uncorrelated Gaussian energy disorder famously explains the origin of non-Arrhenius $\exp [-\sigma^2/(k_{B}T^2)]$ temperature dependence in disordered systems.Here we show that unbiased diffusion remains asymptotically normal also in the presence of spatia
correlations decaying to zero. However, because of a temporal lack of self-averaging, transient subdiffusion emerges on the mesoscale, and it can readily reach macroscale even for moderately strong disorder fluctuations of $\sigma\sim 4 - 5k_{B}T$. Because of its nonergodic origin, such subdiffusion exhibits a large scatter in single-trajectory averages. However, at odds with intuition, it occurs essentially faster than one expects from the normal diffusion in the absence of correlations. We apply these results to diffusion of regulatory proteins on DNA molecules and predict that such diffusion should be anomalous, but much faster than earlier expected on a typical length of genes for a realistic energy disorder of several room $k_{B}T$, or merely 0.05–0.075 eV.

Igor Goychuk, Vasyl O. Kharchenko. Anomalous Features of Diffusion in Corrugated Potentials with Spatial Correlations: Faster than Normal, and Other Surprises, Physical Review Letters, 113, 100601 (2014)

## Subdiffusive rocking ratchets in viscoelastic media: Transport optimization and thermodynamic efficiency in overdamped regime

We study subdiffusive overdamped Brownian ratchets periodically rocked by an external zero-mean force in viscoelastic media within the framework of a non-Markovian generalized Langevin equation approach and associated multidimensional Markovian embedding dynamics. Viscoelastic deformations of the medium caused by the transport particle are modeled by a set of auxiliary Brownian quasiparticles elastically coupled to the transport particle and characterized by a hierarchy of relaxation times which obey a fractal scaling. The most slowly relaxing deformations which cannot immediately followto the moving particle imprint long-range memory about its previous positions and cause subdiffusion and anomalous transport on a sufficiently long time scale. This anomalous behavior is combined with normal diffusion and transport on an initial time scale of overdamped motion. Anomalously slowdirected transport in a periodic ratchet potentialwith broken space inversion symmetry emerges due to a violation of the thermal detailed balance by a zero-mean periodic driving and is optimized with frequency of driving, its amplitude, and temperature. Such optimized anomalous transport can be low dispersive and characterized by a large generalized Peclet number. Moreover, we show that overdamped subdiffusive ratchets can sustain a substantial load and do useful work. The corresponding thermodynamic efficiency decays algebraically in time since the useful work done against a load scales sublinearly with time following to the transport particle position, but the energy pumped by an external force scales with time linearly. Nevertheless, it can be transiently appreciably high and compare well with the thermodynamical efficiency of the normal diffusion overdamped ratchets on sufficiently long temporal and spatial scales.

Vasyl O. Kharchenko, Igor Goychuk Subdiffusive rocking ratchets in viscoelastic media: Transport optimization and thermodynamic efficiency in overdamped regime PHYSICAL REVIEW E 87, 052119 (2013)

### Our Team

• ##### Dmytro Kharchenko

Head of the dept., Dr.Sci.,  Professor

Dr.Sci.,  Professor

• ##### Serhiy Kokhan

PhD, Research fellow

• ##### Vasyl Kharchenko

Phd, Research fellow

• ##### Iryna Lysenko

PhD, Research fellow

• ##### Olga Shchokotova

PhD, Research fellow

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