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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.