Sphingomyelin is much more effective than saturated phosphatidylcholine in excluding unsaturated phosphatidylcholine from domains formed with cholesterol.

In this study, we compared domain formation in raft-like mixtures of cholesterol and dioleoylphosphatidylcholine (DOPC) with either sphingomyelin (SM) or dipalmitoylphosphatidylcholine (DPPC). Using 2H nuclear magnetic resonance, we studied the properties of the lipid enriched in the fluid phase, DOPC. We found that acyl chain 2H-labeled DOPC is much less ordered in SM-containing mixtures than in those containing DPPC, suggesting that DOPC in the SM-containing mixture senses a lower concentration of cholesterol in its direct environment. Atomic force microscopy experiments demonstrated large differences in the size and shape of domains in the different mixtures. We propose that these various differences are a consequence of the preferential interaction of cholesterol for sphingolipids over glycerophospholipids.