Bending-torsional elasticity and energetics of the plus-end microtubule tip

Abstract

Microtubules (MTs), mesoscopic cellular filaments, grow primarily by the addition of GTP-bound tubulin dimers at their dynamic flaring plus-end tips. They operate as chemomechanical energy transducers with stochastic transitions to an astounding shortening motion upon hydrolyzing GTP to GDP. Time-resolved dynamics of the MT tip—a key determinant of this behavior—as a function of nucleotide state, internal lattice strain, and stabilizing lateral interactions have not been fully understood. Here we use atomistic simulations to study the spontaneous relaxation of complete GTP-MT and GDP-MT tip models from unfavorable straight to relaxed splayed conformations and to comprehensively characterize the elasticity of MT tips. Our simulations reveal the dominance of viscoelastic dynamics of MT protofilaments during the relaxation process, driven by the stored bending-torsional strain and counterbalanced by the interprotofilament interactions. We show that the posthydrolysis MT tip is exposed to higher activation energy barriers for straight lattice formation, which translates into its inability to elongate. Our study provides an information-driven Brownian ratchet mechanism for the elastic energy conversion and release by MT tips and offers insights into the mechanoenzymatics of MTs.