Tubulin shape controls the kinetics and mechanism of microtubule depolymerization*

Microtubules exhibit alternating phases of growth and shrinkage thought to be controlled by the conformation of tubulin dimers. Specifically, compression of tubulin due to the hydrolysis of GTP has been suggested to generate stress and drive catastrophic depolymerization. We use molecular dynamics simulations and ex vivo experiments to investigate how depolymerization is affected by the presence of uncompressed (unhydrolysed) dimers in the microtubule lattice. Both methods reveal exponential decay in the kinetics of depolymerization corresponding to the relative number of uncompressed dimers. This slowdown is accompanied by a morphological change from ram's horns to blunt-ended dissociation. Collectively these data show that uncompressed dimers can alter depolymerization consistent with promoting rescue events.