Exploring Microtubule Structural Mechanics through Molecular Dynamics Simulation

Microtubules (MTs), polymerized from dimer units, are the main cytoskeletal filaments providing structural support for cells. The reorganization of MTs is often initiated by removing dimers through mechanical destruction of motor enzymes, such as katanin and spastin severing enzymes. Those enzymes convert chemical energy from ATP hydrolysis into mechanical work. The previous experimental work suggests that lattice defects act as active spots for those enzymes working on the MT lattice. In our research, we investigate the mechanical behavior leading to the crushing and recovering of MTs through using molecular dynamics simulations. Our in-silico experiments provide details of the MT breaking pathways at the molecular level as well as the distribution of mechanical forces needed to break the lattice. Our results strongly confirm the proposal that defects represented by lattice vacancies are important in MT crushing, as the force needed to break a filament with vacancies is much lower than it required to break an intact one. We obtained an exact match between our results and their experimental counterparts, including the force response, the breaking pathways and the respective kinking angle distributions, etc. We also studied the recovery process of MTs with or without vacancies and in the presence and absence of constraints. Our results indicate that constraints prevent MTs from fully recovering, particularly for a lattice with a high degree of vacancies. Taken together with the pushing studies, our lattice recovery data highly demonstrate the assumption that vacancies in the filament can weaken the MT stability and serve as targets for MT severing enzymes. We probed mechanical properties of the seam, which is usually considered as an inherent structural flaw in MTs. However, in our records, the seam behaved similarly as other lattice interfaces did in indentations as well as retractions. All the evidence convincingly demonstrated that the seam, although structurally different from other lattice regions, cannot be treated as an inherently existing severing site for enzymes.