Dynamic Instability Emerges from Micromechanics and Chemical Kinetics of Microtubule Protofilaments

Abstract

Microtubules are crucial for various cellular processes like chromosome segregation, intracellular transport, and cell motility. They are known to display cycles of consistent growth and rapid shrinkage in a phenomenon called dynamic instability. The dynamic instability is attributed to the coupling between chemical kinetics and mechanics of its constituent protofilaments. To develop a mechanistic understanding of the microtubule dynamics and its regulation, we study a mechanochemical model that takes into account a coarse-grained description of the mechanics of microtubule protofilaments in the presence of thermal fluctuations along with association-dissociation kinetics and hydrolysis of tubulin subunits. Our simple model allowed us to simulate and evaluate various mechanisms of catastrophe and rescue in microtubules for a large range of parameters. We found a range of parameters for which the characteristics length- and time-scales associated with microtubule dynamics naturally emerge from our mechanochemical model. Furthermore, our analysis provides novel insights into how the distribution of GTP subunits along the microtubule influences catastrophe and rescue during the dynamic instability.