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 C(0) (monolayer spontaneous curvature) is the major factor dictating fusion, owing to the associated variation in G(E)s (elastic energies) of the fusion intermediates (e.g. stalk). By exploring the correlations among fusion, C(0) 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 C(0) but also K(cp) variations affect fusion, with depression in K(cp) leading to suppression in fusion. Variations in G(E)s and inter-membrane interactions cannot account for the K(cp)-fusion correlation; fusion is suppressed even as the G(E)s decrease with K(cp), indicating the presence of factor(s) with fusogenic importance overtaking that of G(E). Furthermore, analyses find that the C(0) 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.