Cytoskeletal filaments, such as microtubules (MTs), have a variety of cellular roles. They serve as tracks for molecular motor transport, participate in cell division, and are regulated by a diverse range of associated proteins. The ability to perform all these roles depends on the mechanical properties of the MTs, which are based on the MT lattice structure, and modulated by molecular motors and MT associated proteins. Our previous simulations showed that the mechanical response of a tubulin dimer and an MT protofilament (PF) is highly sensitive to the orientation and point of application of external forces. Here, we focus on the effect of varying the length and degree of complexation of an MT PF. In particular, we studied a complex of MT PFs, consisting of three PFs joined together by lateral contacts. We found that the flexibility of PFs, as determined by the spring constant in the linear regime of bending, increases with PF length. Our most striking result is that the addition of the lateral interfaces, which represent the weakest interactions in the MT lattice, has a significant effect on the mechanics of the system. Namely, the energy required to depolymerize the PF decreases dramatically compared to the energy required to depolymerize an isolated PF. This is due to crowding effects similar to the behavior of protein folding in the cellular environment, and is manifested as a high degree of cooperativity between the lateral and longitudinal interfaces in the full MT cylinder. Ultimately, our results are relevant for understanding the mechanism of severing enzymes such as spastin and katanin.

Modeling the effect of length and crowding on the mechanics of microtubule protofilaments

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.