Effects of microtubule mechanics on hydrolysis and catastrophes

TL;DR

This paper presents a mechanical model of microtubules that links lateral bonds, bending rigidity, and steric interactions to hydrolysis and catastrophe dynamics, revealing how mechanical forces influence microtubule stability and behavior.

Contribution

It introduces a novel allosteric model incorporating mechanical forces into microtubule hydrolysis and catastrophe analysis, highlighting correlation effects and rupture thresholds.

Findings

Mechanical energies modulate hydrolysis rates.

Identification of initiation configurations for catastrophes.

Avalanche-like catastrophe events triggered by lateral bond rupture.

Abstract

We introduce a model for microtubule mechanics containing lateral bonds between dimers in neighboring protofilaments, bending rigidity of dimers, and repulsive interactions between protofilaments modeling steric constraints to investigate the influence of mechanical forces on hydrolysis and catastrophes. We use the allosteric dimer model, where tubulin dimers are characterized by an equilibrium bending angle, which changes from $0^\circ$ to $22^\circ$ by hydrolysis of a dimer. This also affects the lateral interaction and bending energies and, thus, the mechanical equilibrium state of the microtubule. As hydrolysis gives rise to conformational changes in dimers, mechanical forces also influence the hydrolysis rates by mechanical energy changes modulating the hydrolysis rate. The interaction via the microtubule mechanics then gives rise to correlation effects in the hydrolysis dynamics, which have not been taken into account before. Assuming a dominant influence of mechanical energies on hydrolysis rates, we investigate the most probable hydrolysis pathways both for vectorial and random hydrolysis. Investigating the stability with respect to lateral bond rupture, we identify initiation configurations for catastrophes along the hydrolysis pathways and values for a lateral bond rupture force. If we allow for rupturing of lateral bonds between dimers in neighboring protofilaments above this threshold force, our model exhibits avalanche-like catastrophe events.