Dynamin optimizes protein-membrane interactions for fission

Abstract Membrane tube fission is a fundamental cellular process, facilitated by the dynamin protein family. The primary energetic barrier to fission arises from the collapse of the tube into a hemifission intermediate or wormlike micelle – an event that constriction helps catalyze. Yet, the precise mechanisms by which dynamin promotes this transition remain unclear. Using self-consistent field theory (SCFT), we model membrane tubes in the presence of dynamin-like proteins, incorporating both steric constriction and surface interactions, enabling us to both model and optimize protein characteristics in order to minimize the fission barrier. We systematically explore the effect of different protein-membrane interaction mechanisms, including excluded volume, head-group adhesion, and leaflet splay, on the fission barrier. Optimizing these parameters to minimize the fission barrier converges to a structure resembling the PH domain of dynamin. While attraction to the surface of the membrane is necessary for protein assembly and induces curvature, it also opposes local constriction, inhibiting tube collapse. In contrast, insertion of the PH domain into the head groups leads to their splaying, producing a localized chevron-shaped membrane deformation. In addition to curvature enhancement, this positions the constriction and fission site adjacent to the protein, allowing fission to proceed without requiring membrane-protein detachment.