Cells exert tight control over the fusion of lipid membranes to enable necessary fusion processes while otherwise maintaining membrane integrity. How proteins then selectively facilitate membrane fusion is an active field of study. However, the elasticity of the lipid membrane itself contributes significantly to the free energy of fusion and its barriers. Nature then has incentive to tune the membrane's elastic properties via lipid composition to aid or inhibit fusion. Similarly, the design of lipid nanoparticles for drug delivery requires the same consideration to aid fusion to the endosomal membrane and the subsequent escape of the drug. In spite of this great practical relevance, study of membrane fusion in simulation or experiment where the elastic parameters are fully known has been elusive, largely due to the difficulty in measuring the Gaussian curvature modulus. This quantity only contributes to the free energy of topological deformations, which is exactly why it is both difficult to measure and of fundamental importance to membrane fusion. Here, we use a novel method to measure the Gaussian curvature modulus, recently developed by us in separate work. By varying the shape of coarse-grained lipids and the temperature of the system, we tune the membrane Gaussian curvature modulus along with the ordinary bending modulus and the spontaneous monolayer curvature. We then simulate multiple vesicle-planar fusion events for a selected set of parameter combinations. The dependence of membrane fusion on each parameter is thus revealed through the observed fusion time, probability, and intermediate structures.
Gallagher et al. (Sun,) studied this question.