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Cellular membrane separates the cytosol from the extracellular space and contains the molecules that facilitate transmission of life-sustaining signals exhibiting lateral heterogeneity through the compartmentalization of lipids, proteins, and carbohydrate molecules. Micro-domains of cholesterol and sphingolipid-rich membranes, called lipid rafts, have attracted much attention from their critical roles in cellular processes through the structural organization and the regulation of protein activation, signaling, and pathogenesis/treatment of neurological and psychiatric disorders. Using supported lipid membranes on wedge-shape substrates with alternating positive and negative curvatures, we represent the curvature-mediated asymmetry of lipid raft domains across the membrane leaflets accompanied by glycolipid receptor localization such as GM1 and GT1b. The raft domains initially appear only in membrane leaflets possessing negative curvature. In the presence of the inter-leaflet coupling, they evolve to generate the transverse registry across the membrane bilayer. We show that a human recombinant anti-body rHIgM12, known to be therapeutic in a mouse model of a neurologic disease, 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. Our methodological platform is a powerful tool of clarifying the mechanism for the leaflet asymmetry and lipid sorting in terms of the membrane curvature, the composition, and the receptor presentation.
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