Sterol structure and sphingomyelin acyl chain length modulate lateral packing elasticity and detergent solubility in model membranes.
Membrane microdomains, such as caveolae and rafts, are enriched in cholesterol and sphingomyelin, display liquid-ordered phase properties, and putatively function as protein organizing platforms. The goal of this investigation was to identify sterol and sphingomyelin structural features that modulate surface compression and solubilization by detergent because liquid-ordered phase displays low lateral elasticity and resists solubilization by Triton X-100. Compared to cholesterol, sterol structural changes involved either altering the polar headgroup (e.g., 6-ketocholestanol) or eliminating the isooctyl hydrocarbon tail (e.g., 5-androsten-3beta-ol). Synthetic changes to sphingomyelin resulted in homogeneous acyl chains of differing length but of biological relevance. Using a Langmuir surface balance, surface compressional moduli were assessed at various surface pressures including those (pi > or =30 mN/m) that mimic biomembrane conditions. Sphingomyelin-sterol mixtures generally were less elastic in a lateral sense than chain-matched phosphatidylcholine-sterol mixtures at equivalent high sterol mole fractions. Increasing content of 6-ketocholestanol or 5-androsten-3beta-ol in sphingomyelin decreased lateral elasticity but much less effectively than cholesterol. Our results indicate that cholesterol is ideally structured for maximally reducing the lateral elasticity of membrane sphingolipids, for enabling resistance to Triton X-100 solubilization, and for interacting with sphingomyelins that contain saturated acyl chains similar in length to their sphingoid bases.
Li
Xin-Min
XM
The Hormel Institute, University of Minnesota, Austin, Minnesota 55912-3698, USA.
Momsen
Maureen M
MM
Brockman
Howard L
HL
Brown
Rhoderick E
RE
D015114:Androstenediol / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D003902:Detergents / Q000494:pharmacology*; D007653:Ketocholesterols / Q000737:chemistry; D008027:Light; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry; D017830:Octoxynol / Q000494:pharmacology; D010100:Oxygen / Q000737:chemistry; D011312:Pressure; D012542:Scattering, Radiation; D013109:Sphingomyelins / Q000737:chemistry*; D013261:Sterols / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
D003902:Detergents; D007653:Ketocholesterols; D008051:Lipid Bilayers; D008055:Lipids; D013109:Sphingomyelins; D013261:Sterols; C063833:6-ketocholestanol; D017830:Octoxynol; D015114:Androstenediol; D002784:Cholesterol; D010100:Oxygen