Elucidating the Origin of Heterogeneous Anomalous Diffusion in the Cytoplasm of Mammalian Cells

TL;DR

This study investigates the mechanisms behind heterogeneous anomalous diffusion in mammalian cell cytoplasm, revealing microtubule-dependent subdiffusion and stochastic switching between mobility states explained by an intermittent fractional Brownian motion model.

Contribution

The paper provides the first comprehensive experimental and theoretical analysis linking heterogeneous anomalous diffusion to intermittent fractional Brownian motion in living cells.

Findings

Microtubule-dependent subdiffusion observed in particle trajectories.

Particles switch stochastically between different mobility states.

Intermittent fractional Brownian motion explains all experimental observations.

Abstract

Diffusion of tracer particles in the cytoplasm of mammalian cells is often anomalous with a marked heterogeneity even within individual particle trajectories. Despite considerable efforts, the mechanisms behind these observations have remained largely elusive. To tackle this problem, we performed extensive single-particle tracking experiments on quantum dots in the cytoplasm of living mammalian cells at varying conditions. Analyses of the trajectories reveal a strong, microtubule-dependent subdiffusion with antipersistent increments and a substantial heterogeneity. Furthermore, particles stochastically switch between different mobility states, most likely due to transient associations with the cytoskeleton-shaken endoplasmic reticulum network. Comparison to simulations highlight that all experimental observations can be fully described by an intermittent fractional Brownian motion, alternating between two states of different mobility.