Revisit the Correlation between the Elastic Mechanics and Fusion of Lipid Membranes

Membrane fusion is a vital process in key cellular events. The fusion capability of a membrane depends on its elastic properties and varies with its lipid composition. It is believed that as the composition varies, the consequent change in C₀ (monolayer spontaneous curvature) is the major factor dictating fusion, owing to the associated variation in G_Es (elastic energies) of the fusion intermediates (e.g. stalk). By exploring the correlations among fusion, C₀ and K_cp (monolayer bending modulus), we revisit this long-held belief and re-examine the fusogenic contributions of some relevant factors. We observe that not only C₀ but also K_cp variations affect fusion, with depression in K_cp leading to suppression in fusion. Variations in G_Es and inter-membrane interactions cannot account for the K_cp-fusion correlation; fusion is suppressed even as the G_Es decrease with K_cp, indicating the presence of factor(s) with fusogenic importance overtaking that of G_E. Furthermore, analyses find that the C₀ influence on fusion is effected via modulating G_E of the pre-fusion planar membrane, rather than stalk. The results support a recent proposition calling for a paradigm shift from the conventional view of fusion and may reshape our understanding to the roles of fusogenic proteins in regulating cellular fusion machineries.