Anomalous intracellular transport phases depend on cytoskeletal network features.

Abstract

Intracellular transport in eukaryotic cells consists of phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton. The interplay between superdiffusive transport along cytoskeletal filaments and the anomalous nature of subdiffusion in the bulk can lead to novel effects in transport behavior at the cellular scale. Here we develop a computational model of the process with cargo being ballistically transported along explicitly modeled cytoskeletal filament networks and passively transported in the cytoplasm by a subdiffusive continuous-time random walk (CTRW). We show that, over a physiologically relevant range of filament lengths and numbers, the network introduces a filament-length sensitive superdiffusive phase at early times which crosses over to a phase where the CTRW is dominant and produces subdiffusion at late times. We apply our approach to the problem of insulin secretion from cells and show that the superdiffusive phase introduced by the filament network manifests as a peak in the secretion at early times followed by an extended sustained release phase that is dominated by the CTRW process at late times. Our results are consistent with in vivo observations of insulin transport in healthy cells and shed light on the potential for the cell to tune functionally important transport phases by altering its cytoskeletal network.