Effects of Ethanol on Lipid Bilayers Containing Cholesterol, Gangliosides, and Sphingomyelin

Abstract

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)

Internal Trehalose Protects Endocytosis from Inhibition by Ethanol inSaccharomyces cerevisiae

“…Ethanol may substitute for water in this role and, in doing so, alter the structure of the membrane, the interactions between lipids and proteins, and the positioning of these molecules in the membranes (2,8,19). These changes may affect membrane functions, with endocytosis being particularly sensitive to these changes (28).…”

Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase

“…In non-interdigitated phospholipid membranes, ethanol tends to adsorb to the head groups, especially the region near the hydrocarbon chains [38,39]. In particular, the carbonyl groups of the glycerol backbone of phospholipids are thought to be the favored hydrogen bonding sites for ethanol [40]. Ethanol displaces water when it adsorbs to the head group, which increases the head group volume and decreases the order of the hydrocarbon chains [13,41,42].…”

Ethanol-Induced Reorganization of the Liquid-Ordered Phase: Enhancement of Cholesterol−Phospholipid Association

“…Based on such studies, it is now clear that ethanol can induce a disordering of the acyl chains of fluid phospholipids, as well as the formation of an interdigitated gel phase. 3,[11][12][13][14][15][16][17] It is also clear that the presence of high concentrations of cholesterol (≥30 mol%) greatly reduces ethanol's ability to disorder fluid phospholipids. 3,18 From detailed NMR studies, it also appears that ethanol favors binding to lipid membranes near the lipid/water interface, in regions that lie close to the glycerol backbone and the "upper" segments of the hydrocarbon chains of the lipids.…”

“…3,[11][12][13][14][15][16][17] It is also clear that the presence of high concentrations of cholesterol (≥30 mol%) greatly reduces ethanol's ability to disorder fluid phospholipids. 3,18 From detailed NMR studies, it also appears that ethanol favors binding to lipid membranes near the lipid/water interface, in regions that lie close to the glycerol backbone and the "upper" segments of the hydrocarbon chains of the lipids. 3,16,19,20 In the work reported herein, our primary aim was to clarify one fundamentally important issue regarding the interactions between ethanol and lipid membranes, which has not previously been addressed.…”

“…3,18 From detailed NMR studies, it also appears that ethanol favors binding to lipid membranes near the lipid/water interface, in regions that lie close to the glycerol backbone and the "upper" segments of the hydrocarbon chains of the lipids. 3,16,19,20 In the work reported herein, our primary aim was to clarify one fundamentally important issue regarding the interactions between ethanol and lipid membranes, which has not previously been addressed. Specifically, can ethanol alter the organization within the liquid-ordered phase?…”