Differential lipid dynamics regulation by sterols in ceramide and sphingomyelin containing membranes

The role of cholesterol in membrane lipid organization and ordering has been evidenced over the past twenty years. The participation of cholesterol precursors and other cholesterol derivatives in the modulation of cell membrane physicochemical properties is less well documented. Herein, an investigation into the effects of cholesterol, two cholesterol precursors (desmosterol and lanosterol) and two hydroxylated metabolites (24S-hydroxycholesterol and 25-hydroxycholesterol) on membrane dynamics was performed. The differences between sphingomyelin- and ceramide-containing membranes were investigated using membrane models that mimic the plasma membrane. Two fluorescent probes were used to study the ordering power and molecular mobility: Laurdan, a sensor of membrane polarity and lipid order near the lipid head groups, and cholesterol-pyrene, a sensor of order near the center of the membrane. The results showed that the double bond in the sterol tail of desmosterol modified the molecular dynamics near the bilayer center resulting in less order in ceramide membranes than in sphingomyelin membranes. The methyl groups on the sterol rings of lanosterol induced increased polarity and decreased order near the lipid head groups, and the hydroxyl groups in the 24 and 25 carbons of the sterol tail changed membrane properties across the membrane axis in a complex manner. These results suggest that the differences in the intra- and intermolecular hydrogen bonding capacities of ceramide and sphingomyelin with specific sterols are in part responsible for specific physicochemical modifications of membranes properties.