Tunable intracellular transport on converging microtubule morphologies

TL;DR

This paper presents a one-dimensional model of microtubule-based intracellular transport near the MTOC, revealing how attachment/detachment rates and attractor positioning influence transport efficiency and control within cells.

Contribution

The study introduces a novel model incorporating advective and diffusive transport to analyze the tunability of cargo movement near the MTOC in cells.

Findings

MFPT transitions from low to high over specific attachment/detachment rates

Optimal dispersal occurs with asymmetric attractor placement when rates are increased

Escape location sensitivity to attractor position is exponentially high in rare event regimes

Abstract

A common type of cytoskeletal morphology involves multiple converging microbutubules with their minus ends collected and stabilized by a microtubule organizing center (MTOC) in the interior of the cell. This arrangement enables the ballistic transport of cargo bound to microtubules, both dynein mediated transport towards the MTOC and kinesin mediated transport away from it, interspersed with diffusion for unbound cargo-motor complexes. Spatial and temporal positioning of the MTOC allows for bidirectional transport towards and away from specific organelles and locations within the cell and also the sequestering and subsequent dispersal of dynein transported cargo. The general principles governing dynamics, efficiency and tunability of such transport in the MTOC vicinity is not fully understood. To address this, we develop a one-dimensional model that includes advective transport towards an attractor (such as the MTOC), and diffusive transport that allows particles to reach absorbing boundaries (such as cellular membranes). We calculated the mean first passage time (MFPT) for cargo to reach the boundaries as a measure of the effectiveness of sequestering (large MFPT) and diffusive dispersal (low MFPT). The MFPT experiences a dramatic growth in magnitude, transitioning from a low to high MFPT regime (dispersal to sequestering) over a window of cargo attachment/detachment rates that is close to in vivo values. We find that increasing either the attachment or detachment rate, while fixing the other, can result in optimal dispersal when the attractor is placed asymmetrically. Finally, we describe a rare event regime, where the escape location is exponentially sensitive to the attractor positioning. Our results suggest that structures such as the MTOC allow for the sensitive control of the spatial and temporal features of transport and corresponding function under physiological conditions.