The Effect of Ceramide Ratio on the Membrane Curvature of Mimetic Models of Matrix Vesicles

The lipid composition of membrane systems plays a critical role in regulating their structural dynamics and curvature, particularly in the biological context of matrix vesicles (MVs) formation during bone mineralization. Recent evidence suggests that the lipid composition of MVs, particularly the balance between sphingomyelin (SM) and ceramide (CER), influences their curvature and stability. We report on the impact of SM and CER ratios on membrane curvature through surface pressure-area isotherm measurements and molecular dynamics (MD) simulations at atomistic and coarse-grained levels. Our findings reveal that increasing the CER content up to 25% significantly enhances membrane curvature, as demonstrated by changes in experimental compressibility moduli and lateral pressure profiles. The lateral pressure profiles and spontaneous bending moments calculated from MD simulations of osteoblast-mimetic membrane models suggest a strong propensity for curvature, particularly in asymmetrical bilayers. It also reveals the role of CER-rich domains in the stabilization of membrane curvature, potentially facilitating the budding processes critical for MVs formation in osteoblasts. These findings underscore the critical role of lipid composition in the mechanisms driving MVs biogenesis.