Beyond the Tip: Lattice Dynamics, Seams, and the Mechanism of Microtubule Fracture

The structural integrity of microtubules is paramount for cellular function. We present a theoretical analysis of their lattice fracture, focusing on the influence of multiseam structures arising from monomer defects and aiming to provide a more accurate estimation of GDP-lattice parameters. Our findings reveal that seams function as pre-existing pathways that accelerate damage propagation. Consequently, monomer vacancies destabilize the lattice due to the inherent structural loss of tubulin-tubulin contacts and the additive acceleration of fracture through multiple seams. Importantly, the comparison of our simulations with experiments on lattice fracture suggests that the intrinsic ratio of longitudinal to lateral binding energies is bounded at approximately 1.5, challenging previous predictions of lattice anisotropy from tip-growth models and highlighting the urgent need to incorporate into current growth models parameters obtained from lattice dynamics.