Microtubule dynamic instability: A new model with coupled GTP hydrolysis and multistep catastrophe

A key question in understanding microtubule dynamics is how GTP hydrolysis leads to catastrophe, the switch from slow growth to rapid shrinkage. We first provide a review of the experimental and modeling literature, and then present a new model of microtubule dynamics. We demonstrate that vectorial, random, and coupled hydrolysis mechanisms are not consistent with the dependence of catastrophe on tubulin concentration and show that, although single‐protofilament models can explain many features of dynamics, they do not describe catastrophe as a multistep process. Finally, we present a new combined (coupled plus random hydrolysis) multiple‐protofilament model that is a simple, analytically solvable generalization of a single‐protofilament model. This model accounts for the observed lifetimes of growing microtubules, the delay to catastrophe following dilution and describes catastrophe as a multistep process.