Cytoskeletal network morphology regulates intracellular transport dynamics

TL;DR

This study investigates how the structure of cytoskeletal networks influences intracellular transport efficiency, revealing that network localization, filament mass, polarity, and motor dynamics critically affect transport times and robustness.

Contribution

It provides new insights into how cytoskeletal topology regulates transport, highlighting the importance of filament distribution, polarity, and motor kinetics in optimizing cellular cargo delivery.

Findings

Network localization near the nucleus minimizes transport time.

Filament mass is the primary factor affecting transit times.

Filament traps cause significant variations in transport efficiency.

Abstract

Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable time scales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design.