Activation of Membrane Fission by Local Elastic Energy Increase at the Edge of Dynamin

Abstract

Membrane fission requires the constriction and breakage of a transient neck, splitting one membrane compartment into two. In endocytosis, the GTPase Dynamin forms a helical coat that constricts membrane necks of Clathrin-coated pits to promote their fission. Dynamin constriction is necessary but not sufficient, questioning the minimal requirements for fission. Here we show that fission occurs at the edge of the Dynamin coat, where it is connected to the uncoated membrane. At this location, the specific shape of the membrane increases locally its elastic energy, facilitating fission by reducing its energy barrier. We predict that fission kinetics should depend on tension, bending rigidity and the Dynamin constriction torque. We verify that fission times depend on membrane tension in controlled conditions in vitro and in Clathrin-mediated endocytosis in vivo. By numerically estimating the energy barrier from the increased elastic energy, and measuring the Dynamin torque, we show that: 1- Dynamin torque, ≈1nN.nm, is huge but necessary to achieve constriction, and 2- Dynamin work sufficiently reduces the energy barrier to promote spontaneous fission.