Role of substrate cooperativity and motor concentration in microtubule severing

Microtubules (MTs) associated proteins (MAPs) regulate the dynamic behavior of MTs during cellular processes. Severing enzymes are MAPs which destabilize MTs by removing subunits from the filament. Because severing enzymes belong to the AAA+ unfoldases family, we probed the severing mechanism characterized by the enzymes applying pulling forces on the C-terminal regions of MT subunits. Due to the large size of the system, we employed coarse grained molecular simulations of different MT lattices and at varying concentration of severing enzymes. Comparison of results from our simulations with data from in-vitro severing assays shows that the cooperative removal of protofilament fragments, at increased concentration of severing enzymes, is a likely MT destabilization scenario. Moreover, we found that optimization of energetics is not a strong requirement if severing proceeds entirely by an unfoldase mechanism.