Tuning of membrane electrostatic properties by single chain sphingolipids sphingosine and sphingosine-1-phosphate: The effect on bilayer dipole potential

Abstract

Abstract An important question in membrane biological chemistry is whether bioactive signaling lipids act only as second messenger ligands or also through an effect on bilayer physical properties. Sphingosine (Sph) and sphingosine-1-phosphate (S1P) are single-chained charged sphingolipids that have antagonistic functions in the “sphingolipid rheostat” which determines cell fate. Sph and S1P respectively promote apoptosis and cell growth. In the present study, the effects of these bioactive lipids on the dipole potential of the lipid bilayer were evaluated. We have investigated the effect of both sphingolipids, incorporated separately or together, in large egg phosphadidylcholine (EPC) unilamellar vesicles on the fluorescence of di-8-ANEPPS, a probe of dipole potential. Both sphingolipids promote a decrease of the dipole potential which is more pronounced for Sph than for S1P. This can be explained by the polarization properties of both the single-chain sphingoid backbone and its surrounding water molecules, as well as by the opposite net charges of the two sphingolipids. When both sphingolipids are present together, as occurs physiologically, the dipole potential varies monotonously over a significant range as a function of the Sph/S1P ratio. This suggests that both sphingolipids are able to tune the dipole potential of cell membranes as a function of their ratio, thereby possibly influencing the binding of surface proteins and the activity of transmembrane proteins. This furthers the idea that the two sphingolipids might exert their biological activity not only as second messenger ligands but also through their effect on lipid membrane physicochemical properties.