title: Oleic- and docosahexaenoic acid-containing phosphatidylethanolamines differentially phase separate from sphingomyelin.
abstract: A central tenet of the lipid raft model is the existence of non-raft domains. In support of this view, we have established in model membranes that a phosphatidylethanolamine (PE)-containing docosahexaenoic acid (DHA) forms organizationally distinct non-raft domains in the presence of sphingomyelin (SM) and cholesterol (Chol). We have shown that formation of DHA-rich domains is driven by unfavorable molecular interactions between the rigid Chol molecule and the highly flexible DHA acyl chain. However, the molecular interactions between SM and the DHA-containing PE, which could also contribute to the formation of DHA-rich non-raft domains, have not been sufficiently investigated. To address this issue, we use differential scanning calorimetry (DSC) to study the phase behavior of mixtures of SM with either 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0-22:6PE) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0-18:1PE), an oleic acid (OA)-containing control, over a wide range of concentrations. Deconvolution of binary DSC scans shows that both 16:0-22:6PE and 16:0-18:1PE phase separate from SM. Analysis of transition temperatures and partial phase diagrams, constructed from the DSC scans for the first time, shows that 16:0-22:6PE displays greater non-ideal mixing with SM compared to 16:0-18:1PE. Our findings support a model in which DHA- and OA-containing PEs differentially phase separate from SM over a wide range of molar ratios to initiate the formation of non-raft domains, which is greatly enhanced by DHA, but not OA, in the presence of cholesterol.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA. shaikhsa@ecu.edu
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Locascio
authors.forename: Smita P
authors.initials: SP
authors.lastname: Soni
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wassall
authors.forename: William
authors.initials: W
authors.lastname: Stillwell
mesh_terms: D002152:Calorimetry, Differential Scanning; D004281:Docosahexaenoic Acids / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry*; D044367:Phase Transition; D013109:Sphingomyelins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D013109:Sphingomyelins; D004281:Docosahexaenoic Acids; D019301:Oleic Acid