Cholesterol decreases the interfacial elasticity and detergent solubility of sphingomyelins

The interfacial interactions of cholesterol with sphingomyelins (SMs) conta ining various homogeneous acyl chains have been investigated by Langmuir fi lm balance approaches. Low in-plane elasticity among the packed lipids was identified as an important physical feature of the cholesterol-sphingomyeli n liquid-ordered phase that correlates with detergent resistance, a charact eristic property of sphingolipid-sterol. rafts. Changes in the in-plane ela stic packing, produced by cholesterol, were quantitatively assessed by the surface compressional moduli (C-s(-1)) of the monolayer isotherms. Of speci al interest were C-s(-1) values determined at high surface pressures (>30 m N/m) that mimic the biomembrane situation. To identify structural features that uniquely affect the in-plane elasticity of the sphingomyelin-cholester ol lateral interaction, comparisons were made with phosphatidylcholine (PC) -cholesterol mixtures. Cholesterol markedly decreased the in-plane elastici ty of either SM or PC regardless of whether they were fluid or gel phase wi thout cholesterol, The magnitude of the reduction in in-plane elasticity in duced by cholesterol was strongly influenced by acyl chain structure and by interfacial functional groups. Liquid-ordered phase formed at lower choles terol mole fractions when SM's acyl chain was saturated rather than monouns aturated. At similar high cholesterol mole fractions, the in-plane elastici ty within SM-cholesterol liquid-ordered phase was significantly lower than that of PC-cholesterol liquid-ordered phase, even when PCs were chain-match ed to the SMs, Sphingoid-base functional groups (e.g., amide linkages), whi ch facilitate or strengthen intermolecular hydrogen bonds, appear to be imp ortant for forming sphingomyelin-cholesterol, liquid-ordered phases with es pecially low in-plane elasticity. The combination of structural features th at predominates in naturally occurring SMs permits very effective resistanc e to solubilization by Triton X-100.