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

Abstract

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.

Mechanisms Underlying Anomalous Diffusion in the Plasma Membrane

“…A feasible origin for fBM is diffusion in a viscoelastic medium, which can arise from very densely crowded environments (Bronstein et al, 2009;Ernst, Hellmann, Kohler, & Weiss, 2012;Goychuk, Kharchenko, & Metzler, 2014;Szymanski & Weiss, 2009). In an elastic material such as a perfect spring, the stress is proportional to strain, i.e., the restoring force linearly increases with the deformation length.…”

Modeling magnetosensitive ion channels in the viscoelastic environment of living cells

“…Diffusion becomes again normal on the time scale t τ h = τ l b N −1 , and η α = η eff τ α−1 h /g α , with a proportionality coefficient g α about unity, g α ∼ 1 [71]. For example, g α ≈ 0.93, for α = 0.4 and N ≥ 5 [72] .…”

“…It has also been generalized to include negative correlations of stochastic force and corresponding memory effects leading to superdiffusion and supertransport [64]. The utility of this approach has been demonstrated on various basic models of nonlinear stochastic dynamics such as bistable dynamics [47], washboard dynamics [47,48,65], anomalous rocking ratchets [48,[66][67][68][69], anomalous flashing ratchets [70], and also in applications to molecular motor dynamics in viscoelastic cytosol [71][72][73].…”

Statistical Properties of a Polymer Chain in the Environment with Low Concentration of Nanoparticles

“…The living cell is a crowded environment filled with particles smaller or larger than protein or DNA chain. The large crowding in the cellular environment affects the diffusivity of both small and large molecules and the motions of molecules are complicated [5]. In the similar way, the translocation of polymer through nanopore, a ubiquitous process in chemical and biological systems, was also influenced by crowding [6].…”