Local Motion Analysis Reveals Impact of the Dynamic Cytoskeleton on Intracellular Subdiffusion

Abstract

Intracellular transport is a complex interplay of ballistic transport along filaments and of diffusive motion, reliably delivering material and allowing for cell differentiation, migration, and proliferation. The diffusive regime, including subdiffusive, Brownian, and superdiffusive motion, is of particular interest for inferring information about the dynamics of the cytoskeleton morphology during intracellular transport. The influence of dynamic cytoskeletal states on intracellular transport are investigated in Dictyostelium discoideum cells by single particle tracking of fluorescent nanoparticles, to relate quantitative motion parameters and intracellular processes before and after cytoskeletal disruption. A local mean-square displacement (MSD) analysis separates ballistic motion phases, which we exclude here, from diffusive nanoparticle motion. In this study, we focus on intracellular subdiffusion and elucidate lag-time dependence, with particular focus on the impact of cytoskeleton compartments like microtubules and actin filaments. This method proves useful for binary motion state distributions. Experimental results are compared to simulations of a data-driven Langevin model with finite velocity correlations that captures essential statistical features of the local MSD algorithm. Specifically, the values of the mean MSD exponent and effective diffusion coefficients can be traced back to negative correlations of the motion's increments. We clearly identify both microtubules and actin filaments as the cause for intracellular subdiffusion and show that actin-microtubule cross talk exerts viscosifying effects at timescales larger than 0.2 s. Our findings might give insights into material transport and information exchange in living cells, which might facilitate gaining control over cell functions.