title: Interaction of cholesterol with a docosahexaenoic acid-containing phosphatidylethanolamine: trigger for microdomain/raft formation?
abstract: Docosahexaenoic acid (DHA, 22:6) containing phospholipids have been postulated to be involved in promoting lateral segregation within membranes into cholesterol- (CHOL-) rich and CHOL-poor lipid microdomains. Here we investigated the specific molecular interactions of phospholipid bilayers composed of 1-[(2)H(31)]palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0-22:6PE-d(31)) or 1-[(2)H(31)]palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0-18:1PE-d(31)) with equimolar CHOL using solid-state (2)H NMR spectroscopy and low- and wide-angle X-ray diffraction (XRD). Moment analysis of (2)H NMR spectra obtained as a function of temperature reveals that the main chain melting transition and the lamellar-to-inverted hexagonal (H(II)) phase transition of 16:0-22:6PE-d(31) remain in the presence of equimolar CHOL, whereas addition of equimolar CHOL essentially obliterates the gel-to-liquid crystalline transition of 16:0-18:1PE-d(31). (2)H NMR order parameter measurements show that the addition of equimolar CHOL in the lamellar liquid crystalline phase causes a smaller increase in order for the perdeuterated sn-1 chain by 22% for 16:0-22:6PE-d(31) as opposed to 33% for 16:0-18:1PE-d(31). XRD experiments determined markedly lower solubility of 32 +/- 3 mol % for CHOL in 16:0-22:6PE bilayers in contrast to the value of approximately 51 mol % for 16:0-18:1PE. Our findings provide further evidence that cholesterol has a low affinity for DHA-containing phospholipids and that this reduced affinity may serve as a mechanism for triggering the formation of lipid microdomains such as rafts.
authors.affiliation: Department of Biology, Indiana University, Indianapolis 46202-5132, USA.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Vadim
authors.initials: V
authors.lastname: Cherezov
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
authors.forename: William
authors.initials: W
authors.lastname: Stillwell
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wassall
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D004281:Docosahexaenoic Acids / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D021962:Membrane Microdomains / Q000737:chemistry*; D008956:Models, Chemical; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: C096034:1-oleoyl 2-docosahexaenoyl phosphatidylethanolamine; C431643:1-stearoyl-2-docosahexaenoyl--sn-glycerophosphoethanolamine; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D004281:Docosahexaenoic Acids; D002784:Cholesterol