Mechanochemical modeling of dynamic microtubule growth involving sheet-to-tube transition

TL;DR

This paper presents a mechanochemical model of microtubule growth, highlighting the role of sheet-to-tube transition and conformational caps in stabilization, independent of GTP hydrolysis, supported by molecular simulations.

Contribution

It introduces a theoretical model of microtubule growth emphasizing mechanical factors and the sheet-to-tube transition, expanding understanding beyond GTP-centric models.

Findings

Minimum conformational cap length for stabilization is two dimers.

Conformational cap functions independently of GTP cap.

Microtubule growth resembles a Tetris-like process regulated by energy and seam zipping.

Abstract

Microtubule dynamics is largely influenced by nucleotide hydrolysis and the resultant tubulin configuration changes. The GTP cap model has been proposed to interpret the stabilizing mechanism of microtubule growth from the view of hydrolysis effects. Besides, the microtubule growth involves the closure of a curved sheet at its growing end. The curvature conversion also helps to stabilize the successive growth, and the curved sheet is referred to as the conformational cap. However, there still lacks theoretical investigation on the mechanical-chemical coupling growth process of microtubules. In this paper, we study the growth mechanisms of microtubules by using a coarse-grained molecular method. Firstly, the closure process involving a sheet-to-tube transition is simulated. The results verify the stabilizing effect of the sheet structure, and the minimum conformational cap length that can stabilize the growth is demonstrated to be two dimers. Then, we show that the conformational cap can function independently of the GTP cap, signifying the pivotal role of mechanical factors. Furthermore, based on our theoretical results, we describe a Tetris-like growth style of microtubules: the stochastic tubulin assembly is regulated by energy and harmonized with the seam zipping such that the sheet keeps a practically constant length during growth.