Cytoskeletal filament length controlled dynamic sequestering of intracellular cargo

TL;DR

This study uses a computational model to explore how filament length and polarity in the cytoskeleton influence dynamic cargo sequestration within cells, revealing an optimal filament length for transport regulation.

Contribution

It introduces a model linking cytoskeletal filament length and polarization to cargo sequestration, highlighting tunable control mechanisms for intracellular transport phases.

Findings

Sequestering regions depend on filament length and polarity.

Cargo residence time varies non-monotonically with filament length.

An optimal filament length enhances cargo sequestration.

Abstract

The spatial localization or sequestering of motile cargo and their dispersal within cells is an important process in a number of physiological contexts. The morphology of the cytoskeletal network, along which active, motor-driven intracellular transport takes place, plays a critical role in regulating such transport phases. Here, we use a computational model to address the existence and sensitivity of dynamic sequestering and how it depends on the parameters governing the cytoskeletal network geometry, with a focus on filament lengths and polarization away or toward the periphery. Our model of intracellular transport solves for the time evolution of a probability distribution of cargo that is transported by passive diffusion in the bulk cytoplasm and driven by motors on explicitly rendered, polar cytoskeletal filaments with random orientations. We show that depending on the lengths and polarizations of filaments in the network, dynamic sequestering regions can form in different regions of the cell. Furthermore, we find that, for certain parameters, the residence time of cargo is non-monotonic with increasing filament length, indicating an optimal regime for dynamic sequestration that is potentially tunable via filament length. Our results are consistent with {\it in vivo} observations and suggest that the ability to tunably control cargo sequestration via cytoskeletal network regulation could provide a general mechanism to regulate intracellular transport phases.