Crowding of molecular motors determines microtubule depolymerization

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.

36 pages, 8 figures

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• Phase-plane analysis of the totally asymmetric simple exclusion process with binding kinetics and switching between antiparallel lanes
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• Exact Large Deviations of the Current in the Asymmetric Simple Exclusion Process with Open Boundaries
• Length regulation of microtubules by molecular motors: Exact solution and density profiles
• Self-organized system-size oscillation of a stochastic lattice-gas model
• Asymmetric Exclusion Process with Global Hopping
• A Bayesian framework for the analog reconstruction of kymographs from fluorescence microscopy data
• Length Regulation Drives Self-Organization in Filament-Motor Mixtures
• Machines of life: catalogue, stochastic process modeling, probabilistic reverse engineering and the PIs- from Aristotle to Alberts
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