A structural mechano-chemical model for dynamic instability of microtubule

Abstract

Microtubules are a major component of the cytoskeleton and vital to numerous cellular processes. The central dogma of microtubules is that all their functions are driven by dynamic instability; understanding its key phenomena (i.e. catastrophe, rescue, pause, differential behaviors at the plus and minus ends) distilled from a myriad of experiments under a consistent and unified scheme, however, has been unattainable. Here, we present a novel statistical-physics-based model uniquely constructed from conformational states deduced from existing tubulin structures, with transitions between them controlled by steric constraints and mechanical energy of the microtubule lattice. This mechano-chemical model allows, for the first time, all the key phenomena of dynamic instability to be coherently reproduced by the corresponding kinetic simulations. Long-puzzling phenomena, such as aging, small GTP-cap size, fast catastrophe upon dilution and temperature-induced ribbon-to-tube transition of GMPCPP-tubulins, robustly emerge and thus can be understood with confidence.