Crowding of molecular motors determines microtubule depolymerization

TL;DR

This study models how crowding of kinesin-8 motors on microtubules regulates their depolymerization, revealing distinct regimes of motor density effects and length-dependent control mechanisms.

Contribution

It introduces an individual-based model showing crowding as the key regulator of microtubule depolymerization, highlighting regimes and the role of motor cooperativity.

Findings

Crowding causes traffic jams affecting depolymerization.

Above a threshold, depolymerization is independent of motor concentration.

Below the threshold, depolymerization depends on motor density and length.

Abstract

Assembly and disassembly dynamics of microtubules (MTs) is tightly controlled by MT associated proteins. Here, we investigate how plus-end-directed depolymerases of the kinesin-8 family regulate MT depolymerization dynamics. Employing an individual-based model, we reproduce experimental findings. Moreover, crowding is identified as the key regulatory mechanism of depolymerization dynamics. Our analysis gives two qualitatively distinct regimes. For motor densities above a particular threshold, a macroscopic traffic jam emerges at the plus-end and the MT dynamics become independent of the motor concentration. Below this threshold, microscopic traffic jams at the tip arise which cancel out the effect of the depolymerization kinetics such that the depolymerization speed is solely determined by the motor density. Because this density changes over the MT length, length-dependent regulation is possible. Remarkably, motor cooperativity does not affect the depolymerization speed but only the end-residence time of depolymerases.