Intrinsic Lipid Curvatures of Mammalian Plasma Membrane Outer Leaflet Lipids and Ceramides

We developed a global X-ray data analysis method to determine the intrinsic curvatures of lipids hosted in inverted hexagonal phases. In particular, we combined compositional modelling with molecular shape-based arguments to account for non-linear mixing effects of guest-in-host lipids on intrinsic curvature. The technique was verified by all-atom molecular dynamics simulations and applied to sphingomyelin and a series of phosphatidylcholines and ceramides with differing composition of the hydrocarbon chains. We report positive lipid curvatures for sphingomyelin and all phosphatidylcholines with disaturated and monounsaturated hydrocarbons. Substitution of the second saturated hydrocarbon with an unsaturated acyl chain in turn shifted the intrinsic lipid curvatures to negative values. All ceramides, with chain lengths varying between C2:0 and C24:0, displayed significant negative lipid curvature values. Moreover, we re-port non-additive mixing for C2:0 ceramide and sphingomyelin. Our findings manifest the high and manifold potential of lipids to modulate physiological membrane function. Highlights Molecular shape based theory for non-linear lipid curvature mixing Global analysis of SAXS patterns inverted hexagonal phases using compositional modelling and Bayesian probability theory MD simulations of inverted hexagonal phases Non-additive mixing of palmitoyl sphingomyelin and C2:0 ceramide