title: Cholesterol interactions with fluid-phase phospholipids: effect on the lateral organization of the bilayer.
abstract: The lateral organization of lipids and proteins in cell membranes is recognized as an important factor in several cellular processes. Cholesterol is thought to function as a modulator of the lateral segregation of lipids into cholesterol-poor and cholesterol-rich domains. We investigated how the affinity of cholesterol for different phospholipids, as seen in cholesterol partitioning between methyl-beta-cyclodextrin and large unilamellar vesicles, was reflected in the lateral organization of lipids in complex bilayers. We especially wanted to determine how the low-T(m) lipid affected the lateral structure. Partition experiments showed that cholesterol had a higher affinity for N-oleoyl-sphingomyelin (OSM) than for palmitoyl-oleoyl-phosphatidylcholine (POPC) bilayers, but the highest preference was for N-palmitoyl-sphingomyelin (PSM)-containing bilayers. Partial phase diagrams of POPC/PSM/cholesterol and OSM/PSM/cholesterol bilayers at 23 degrees C and 37 degrees C were used to gain insight into the lateral organization of lipids in bilayers. Analysis of phase diagrams revealed that the phospholipid composition of cholesterol-poor and cholesterol-rich domains reflected the affinity that cholesterol exhibited toward bilayers composed of different lipids. Therefore, the determined affinity of cholesterol for different phospholipid bilayers was useful in predicting the cholesterol-induced lateral segregation of lipids in complex bilayers.
authors.affiliation: Department of Biochemistry and Pharmacy, Abo Akademi University, FIN-20520 Turku, Finland.
authors.forename: Katrin K
authors.initials: KK
authors.lastname: Halling
authors.forename: Bodil
authors.initials: B
authors.lastname: Ramstedt
authors.forename: Joel H
authors.initials: JH
authors.lastname: Nyström
authors.forename: J Peter
authors.initials: JP
authors.lastname: Slotte
authors.forename: Thomas K M
authors.initials: TK
authors.lastname: Nyholm
mesh_terms: D016880:Anisotropy; D002784:Cholesterol / Q000378:metabolism*; D004161:Diphenylhexatriene / Q000494:pharmacology; D005453:Fluorescence; D008051:Lipid Bilayers / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D044367:Phase Transition / Q000187:drug effects; D010713:Phosphatidylcholines; D010743:Phospholipids / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins; D047392:beta-Cyclodextrins; C033171:palmitoylsphingomyelin; C088515:N-oleoylsphingomyelin; D004161:Diphenylhexatriene; D002784:Cholesterol; C031215:betadex; C028694:1-palmitoyl-2-oleoylphosphatidylcholine