Minimum energy path to membrane pore formation and rupture

We combine dynamic self-consistent field theory with the string method to calculate the minimum energy path to membrane pore formation and rupture. In the regime where nucleation can occur on experimentally relevant time scales, the structure of the critical nucleus is between a solvophilic stalk and a locally thinned membrane. Classical nucleation theory fails to capture these molecular details and significantly overestimates the free energy barrier. Our results suggest that thermally nucleated rupture may be an important factor for the low rupture strains observed in lipid membranes.