Direct NMR Evidence for Ethanol Binding to the Lipid-Water Interface of Phospholipid Bilayers

Abstract

The mechanisms behind the membrane-mediated effects of ethanol were examined via the interaction of ethanol with phospholipid bilayers at hydration levels of 10-12 water molecules per lipid. 2H and 31P nuclear magnetic resonance (NMR) spectroscopy was used to monitor deuterated water and ethanol and the headgroups and acyl chains of neutral phospholipids. Ethanol was found to interact strongly with both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers, giving 2H NMR quadrupolar splittings for CH3CD2OH between 6.3 and 9.4 kHz. The quadrupolar splittings for ethanol in gel-phase lipids remained well resolved and were not significantly larger than those in the L alpha phase, suggesting that little or no ethanol was bound in the hydrocarbon interior of the bilayer. Ethanol binding significantly altered the orientation of the lipid headgroups, as shown with headgroup-deuterated PC bilayers. The entire lengths of the acyl chains were significantly disordered by the ethanol interaction, evidenced by significant reductions in the 2H NMR order parameters of the chains. The disordering corresponds to an increase in the area per lipid by an estimated 6% with one ethanol molecule per lipid, and a total of 18% with a second ethanol per lipid. This pronounced area increase is presumably caused by the disruption of lipid packing in the rigid region of the glycerol backbone rather than in the acyl chains, since the order of hydrocarbon chains is not affected to a significant degree by incorporation of alkanes and long-chain alcohols into the hydrocarbon interior.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour

“…These include the involvement of neuropeptide-Y related pathways, [1][2][3][4] glutamate receptors, 5,6 GABA receptors, 7,8 the cAMP signalling pathway, 9,10 the BK potassium channel, SLO-1 [11][12][13] , and membrane perturbation. 14 Many genes and proteins are conserved between Caenorhabditis elegans and humans, including many of those that have been identified as playing a possible role in the effects of ethanol. 1,13,15 This genetic model therefore potentially provides a powerful new insight into the molecular actions of ethanol through the use of forward genetic screens.…”

Effects of Ethanol and Cholesterol on Thermotropic Phase Behavior of Ion-Pair Amphiphile Bilayers

“…It should be noted that the lack of biphasic dependence on ethanol concentration was also reported in the literature for Pes 28 , phosphatidylserine PS 36 , and PCs with large C values 32 , where C is the effective acyl chain length difference between the sn-1 and sn-2 acyl chains. On the other hand, ethanol binding to the lipid-water interface of phospholipid bilayers may significantly altered the orientation of the bilayer headgroups and disordered the entire lengths of the hydrocarbon chains 37 . Pronounced increase in the area per lipid 37,38 , decrease in the ordering of the chains 37,39 , and higher fluidity and permeability of the bilayers 38,39 were attributed to ethanol and other short-chain alcohols.…”

“…On the other hand, ethanol binding to the lipid-water interface of phospholipid bilayers may significantly altered the orientation of the bilayer headgroups and disordered the entire lengths of the hydrocarbon chains 37 . Pronounced increase in the area per lipid 37,38 , decrease in the ordering of the chains 37,39 , and higher fluidity and permeability of the bilayers 38,39 were attributed to ethanol and other short-chain alcohols. The monotonous lowering of T m exhibited by IPA bilayers, therefore, is possibly due to the same disordering effects of ethanol on lipid bilayers.…”

Synthesis of p-tert-butylthiacalix[4]arenes functionalized with tris(2-aminoethyl)amine fragments at the lower rim and their interaction with model lipid membranes

“…It is known that small amphiphilic molecules are often located in the headgroup domain of lipid membranes. [35][36][37][38][39] Moreover, amphiphilic calixarenes have been shown to be embedded in lipid membranes. [40][41][42][43] Thus, we can assume that compounds 4 and 5 which have distinct hydrophilic and hydrophobic domains are located close to phospholipid phosphate headgroups with their protonated NH 3 + groups forming ion-pairs with the phosphate headgroups in addition to hydrogen bonding between P=O····H-N groups.…”