Docosahexaenoic acid enhances segregation of lipids between : 2H-NMR study.

Solid-state (2)H-NMR of [(2)H(31)]-N-palmitoylsphingomyelin ([(2)H(31)]16:0SM, PSM*), supplemented by differential scanning calorimetry, was used for the first time, to our knowledge, to investigate the molecular organization of the sphingolipid in 1:1:1 mol mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (16:0-18:1PE, POPE) or 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (16:0-22:6PE, PDPE) and cholesterol. When compared with (2)H-NMR data for analogous mixtures of [(2)H(31)]16:0-18:1PE (POPE*) or [(2)H(31)]16:0-22:6PE (PDPE*) with egg SM and cholesterol, molecular interactions of oleic acid (OA) versus docosahexaenoic acid (DHA) are distinguished, and details of membrane architecture emerge. SM-rich, characterized by higher-order, and PE-rich, characterized by lower-order, domains <20 nm in size are formed in the absence and presence of cholesterol in both OA- and DHA-containing membranes. Although acyl chain order within both domains increases on the addition of sterol to the two systems, the resultant differential in order between SM- and PE-rich domains is almost a factor of 3 greater with DHA than with OA. Our interpretation is that the aversion that cholesterol has for DHA--but not for OA--excludes the sterol from DHA-containing, PE-rich (nonraft) domains and excludes DHA from SM-rich/cholesterol-rich (raft) domains. We attribute, in part, the diverse health benefits associated with dietary consumption of DHA to an alteration in membrane domains.