Influence of the Linkage Region of Sphingolipids on Sphingolipid−Phospholipid Mixing in Cholesterol-Rich Bilayers^†

Abstract

The influence of the linkage region of a sphingolipid on its mixing with a phospholipid in cholesterol-rich bilayers has been examined by use of the nearest-neighbor recognition method (Davidson, S. K. M.; Regen, S. L. Chem. Rev. 1997, 97, 1269). Thus, an analysis of equilibrium dimer distributions derived from an exchangeable sphingolipid monomer (SL, made from N-stearoyl-d-erythro-sphinganine) or a phospholipid analogue (PL, made from 1-myristoyl-2-stearoyl-sn-glycero-3-phosphoethanolamine) plus a shorter phospholipid (14, made from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine) has revealed a preference for homolipid association in SL/14-based bilayers; that is, the linkage region of the sphingolipid promotes its segregation from the phospholipid. Inclusion of 20−40 mol % cholesterol increases this preference for homolipid association. The magnitude of this effect is similar to that found in cholesterol-rich bilayers containing two exchangeable phospholipids, which differ in length by four methylene units, that is, 18 (made from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine) and 14. The relevance of these findings to the concept of lipid rafts is briefly discussed