Dynamin Optimizes Protein-Membrane Interactions for Fission

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 hemifused intermediate—an event that constriction helps catalyze. We previously developed a self-consistent field theory (SCFT) framework to systematically study this process, and validated it against experiments (Spencer et al., Nat. Commun. 2024; Biophys. J. 2024). The precise mechanisms by which dynamin promotes this transition, however, remain unclear. Using SCFT, we now model membrane tubes in the presence of dynamin-like proteins, incorporating both steric constriction and surface interactions. We explore the effect of different protein-membrane coupling mechanisms on the fission barrier, including excluded volume, head-group adhesion, and leaflet splay. While membrane attraction is necessary for protein assembly and induces curvature, it also opposes local constriction and inhibits tube collapse. In contrast, insertion of the PH domain into the head groups leads to their splaying and produces a localized chevron-shaped membrane deformation. This enhances curvature and facilitates tube collapse without opposing local constriction, thus promoting fission.