(696d) First Passage of Molecular Motors on Networks of Cytoskeletal Filaments

Molecular motors facilitate intracellular transport by actively transporting cargo along cytoskeletal filaments. The behavior of a motor traversing a single filament has been well-characterized for many motors. However, understanding how motors traverse networks of cytoskeletal filaments remains an open problem with applications in cell biology and the design of active biological materials.

In this work, we use kinetic Monte Carlo computer simulations to investigate the transport of molecular motors across a domain containing a network of filaments. The overall motion consists of passive cytosolic diffusion and directed transport along filaments; the first passage time describes the time for a motor to first traverse the simulation domain. To probe the link between the network structure and long-range motor transport, we systematically vary properties of the network and assess the effect on the distribution of first passage times. For networks of randomly oriented filaments, domains with moderate numbers of long filaments have the largest mean first passage time with the largest coefficient of variation. This is indicative of slow, unreliable transport. Additionally, randomly generated networks with the same number and lengths of filaments can lead to markedly different first passage times, indicating the importance of the underlying filament distribution. Some networks produce anomalously large first passage times. These have spatial regions where motors become trapped for long periods of time. Removal of a small fraction of filaments significantly reduces the mean first passage time, but surprisingly, the most impactful filaments are far removed from the trapping regions. These filaments serve as lynchpins connecting one region to another. We develop analytical theory to describe effective diffusion coefficients and to highlight the importance of long-lived traps.

Taken together, our results relate the first passage of a molecular motor across a domain to features of the underlying filament network. We conclude by discussing implications of our results for plant cell biology, where large cell sizes can lead to prohibitively large diffusive time scales for cell mixing.