Microtubules are prime examples of large-size biomolecular systems that assemble, disassemble, and self-repair by controlled inputs. Despite the known role of mechanics in both the function of microtubules for example as motors driving the poleward chromosome motion during mitosis and in the remodeling of the microtubule lattice during depolymerization and severing by molecular motors, an understanding of the link between the structure of filaments and their dynamical properties is still in its infancy. Establishing such a link requires a combined experimental and computational approach. We will discuss the development of our approach to investigate the mechanics of filaments with relevance for chromosome motion and microtubule severing. Because of the modular architecture and strong inter- and intra-molecular coupling that influence the properties of microtubule filaments, we developed a multi-scale methodology, using coarse-graining and atomic details, to map out mechanical properties of microtubules on experimental timescales through large-scale molecular simulations. Our coarse-grained model reduces the microtubule subunits to polymeric chains characterized by excluded-volume effects and non-covalent interactions between beads undergoing Brownian motion. We will present our findings of the microscopic origin of physico-chemical properties of microtubules and their protofilaments and the molecular mechanisms of their response to controlled mechanical inputs. Our results focus on the thermodynamics of the lattice and the large bending rigidity for a protofilament, which support the idea that the disassembling microtubule is capable of generating a large mechanical force to move chromosomes during cell division. Particular focus will be on the mechanism employed by severing enzymes to tear microtubules apart. Finally, we will discuss the validation of these results through direct comparison with in vitro experiments, indicating that the measured parameters sample the same distributions.

Multi-scale modeling of the nanomechanics of microtubule filaments

2019 Fall National Meeting

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