ATP-Dependent Diffusion Entropy and Homogeneity in Living Cells

Wohl Wohl,Sherman Sherman

doi:10.3390/e21100962

Abstract

Intracellular dynamics is highly complex, and includes diffusion of poly-dispersed objects in a non-homogeneous, out-of-equilibrium medium. Assuming non-equilibrium steady-state, we developed a framework that relates non-equilibrium fluctuations to diffusion, and generalized entropy in cells. We employed imaging of live Jurkat T cells, and showed that active cells have higher diffusion parameters (Kα and α) and entropy relative to the same cells after ATP depletion. Kα and α were related in ATP-depleted cells while this relation was not apparent in untreated cells, probably due to non-equilibrium applied work. Next we evaluated the effect of intracellular diffusion and entropy on the cell content homogeneity, which was displayed by the extent of its liquid–liquid phase separation (LLPS). Correlations between intracellular diffusion parameters, entropy and cell homogeneity could be demonstrated only in active cells while these correlations disappeared after ATP depletion. We conclude that non-equilibrium contributions to diffusivity and entropy by ATP-dependent mechanical work allow cells to control their content homogeneity and LLPS state. Such understanding may enable better intervention in extreme LLPS conditions associated with various cell malignancies and degenerative diseases.

Highlights

Intracellular dynamics is highly complex relative to thermal Brownian motion in a homogeneous viscous fluid
The intracellular medium is considered a non-equilibrium viscoelastic medium with active (ATP-dependent) mechanical fluctuations that contribute to the particle random translocations [7]
We further assume that the cell is in steady-state, since the diffusion process is much faster than global cell dynamics

Summary

Introduction

Intracellular dynamics is highly complex relative to thermal Brownian motion in a homogeneous viscous fluid It includes diffusion of poly-dispersed objects in a non-homogeneous, out-of-equilibrium medium that typically demonstrates viscoelasticity, crowding, confinement and mechanical work, driven by ATP-consumption [1,2,3,4]. The intracellular structure has elastic properties that are non-linear and depend on the amount of load that the cytoskeleton has to resist. It depends on generated forces from ATP-dependent myosin interactions with the actin cytoskeleton mesh [6,8,9]. Inhibition of acto-myosin interactions decreases cell elasticity by about two fold [7]

Methods

Results

Discussion

Conclusion