Dynamic instability from nonequilibrium structural transitions on the energy landscape of microtubule.

Abstract

Microtubules are the backbone of the cytoskeleton and vital to numerous cellular processes. All the functions of microtubules are driven by dynamic instability, but its mechanism has remained unresolved for over 30 years because of conceptual difficulties inherent in the prevalent GTP-cap framework. We present a physically rigorous structural mechano-chemical model: dynamic instability is driven by non-equilibrium transitions between the bent (B), straight (S), and curved (C) structures of tubulin monomers and longitudinal interfaces in the two-dimensional lattice of microtubule. All the different phenomena (growth, shortening, catastrophe, rescue, and pausing) are controlled by the kinetic pathways for B-to-S and S-to-C transitions and their corresponding energy landscapes. Different kinetics of dynamic instability at plus and minus ends are due to different B-to-S and S-to-C pathways necessitated by the polarity of microtubule lattice. This model enables us to reproduce all the observed phenomena of dynamic instability of purified tubulins in kinetic simulations and provide the detailed physical mechanisms behind them.