Effects of ethanol on lipid bilayers containing cholesterol, gangliosides, and sphingomyelin

The influence of lipid composition on the response of bilayers to ethanol binding was investigated with 2H NMR spectroscopy. The bilayers were composed of various combinations of the lipids most often found in neural cell membranes: phosphatidylcholines (PCs), gangliosides, sphingomyelin, and cholesterol. The PCs, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), were chain-perdeuterated to allow the response of bilayer order to ethanol to be monitored at all positions through the depth of the bilayer interior. All bilayers were investigated in the lamellar liquid-crystalline (L alpha) phase. The results from the de-Paked NMR spectra demonstrate that ethanol binding in the lipid-water interface [Barry, J. A., & Gawrisch, K. (1994) Biochemistry 33, 8082-8088] alters order parameter profiles in the bilayer interior differently for the various lipid mixtures. The presence of 10 mol % brain gangliosides enhanced the disordering effect of ethanol and altered the response of the order profile along the PC chains. This effect was apparently caused by sugar-ethanol interactions in the oligosaccharide head group. The impact of the ceramide moiety of brain sphingomyelin (50 mol % in DMPC) was negligible. In bilayers containing cholesterol, the binding of ethanol and its effects on the hydrocarbon interior were found to reflect the phase transition to the liquid-ordered phase at about 25 mol % cholesterol [Thewalt, J. L., & Bloom, M. (1992) Biophys. J. 63, 1176-1181]. Results from the quadrupolar splittings for deuterated ethanol (CH3CD2OH) bound to cholesterol-containing bilayers showed that ethanol binding decreased with increasing amounts of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)