Curvature Elasticity-Driven Leaflet Asymmetry and Interleaflet Raft Coupling in Supported Membranes

Membrane curvature is closely associated with spatial distribution of lipids and curvature can influence the formation of lipid rafts in biological membranes. However, it is still unclear how the curvature elasticity plays a role on the asymmetric distribution of lipids across the membrane leaflets, especially, during the process of the raft domain growth. Using supported lipid membranes on wedge-shaped substrates with alternating positive and negative curvatures, curvature-mediated asymmetry of lipid raft domains is observed across the membrane leaflets accompanied by glycolipid receptor (GM₁ and GT₁b) localization. The raft domains initially appear only in a membrane leaflet possessing negative curvatures. In the presence of the interleaflet coupling, they evolve to generate the transverse registry across the membrane bilayer. It is shown that a human recombinant antibody rHIgM12 is co-localized with the rafts formed at the peaks and valleys of the wedge substrate, indicating that the spatial distribution of its receptor (GT₁b) is indeed manifested by the site-specific formation of asymmetric raft domains through the curvature elasticity. The platform can be used to explore the mechanism for the leaflet asymmetry and lipid sorting in terms of the membrane curvature, the composition, and the receptor presentation.