FIGURE 1.

Steps of the membrane fusion process and considerations on the energy impact of lipid geometry. The fusion process starts by the formation of an hemifused-like structure (only the outer leaflets have merged). This highly curved structure spatially constrains the hydrophilic heads of the lipids that are situated on the outer leaflet. Due to their spontaneous curvature, it is more favorable energetically for conical lipids to adopt this configuration than cylindrical lipids. Fusion is completed by the opening of a pore. At this step, the inner leaflets of the bilayer are now curved, and in this case, it is less favorable for conical lipids to adopt this configuration as their hydrophobic tails are now more accessible to water. On the other hand, malleable lipids could favor any bent configuration as they can adapt their geometry to that of the membrane without significant energy cost.