  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.
