Oleic- and docosahexaenoic acid-containing phosphatidylethanolamines differentially phase separate from sphingomyelin.
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.
Shaikh
Saame Raza
SR
Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA. shaikhsa@ecu.edu
Locascio
Daniel S
DS
Soni
Smita P
SP
Wassall
Stephen R
SR
Stillwell
William
W
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*
D008051:Lipid Bilayers; D013109:Sphingomyelins; D004281:Docosahexaenoic Acids; D019301:Oleic Acid