Contribution of hydrogen bonding to lipid-lipid interactions in membranes and the role of lipid order: Effects of cholesterol, increased phospholipid unsaturation, and ethanol

Abstract

It is proposed that increased phospholipid unsaturation in membranes and perturbation by agents such as ethanol weaken interlipid hydrogen bonding involving water and that the process is independent of effects on lipid order. To investigate this, the rates of phospholipid desorption, as a measure of the strength of interlipid interactions, from "donor" lipid vesicles was determined. This was accomplished using (7-nitrobenzo-2-oxa-1,3-diazole-4-yl)aminohexanoate (C6-NBD) labeled phospholipids, the rate of desorption being followed from changes in fluorescence with time. The rates of desorption of the NBD-phospholipids from phosphatidylcholine (PC) donor vesicles was in the order phosphatidylcholine (PC) > phosphatidylserine (PS) > phosphatidylethanolamine (PE), the slower rates in the PS and PE reflecting direct interlipid hydrogen bonding. For PC, the interlipid hydrogen bonding was restricted to the "hydration layer", the network of hydrogen-bonded water molecules extending between phospholipid head groups. The rate of C6-NBD-PC desorption was elevated with higher levels of donor PC sn-2 unsaturation, due the increased head group spacing weakening the lipid-lipid interactions that occur via the hydration layer. Ethanol also increased the rate of NBD-phospholipid desorption from donor PC vesicles in the order PC > PS > PE, showing that PC interactions, here limited to the weaker hydrogen-bonded water molecule network, were more susceptible compared to stronger, direct interlipid hydrogen bonds involving PE and PS. The relative magnitude of the ethanol-induced increase in the desorption rate was amplified with higher levels of donor lipid sn-2 unsaturation. Cholesterol had little effect on the rate of phospholipid desorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Exploring membrane organization and dynamics by the wavelength-selective fluorescence approach

“…The precise orientation and location of the NBD group of this molecule in the membrane is known London, 1987, 1988;Mitra and Hammes, 1990;Wolf et al, 1992;Abrams and London, 1993). This group has been found to be localized at the membrane interface which has unique motional and dielectric characteristics distinct from both the bulk aqueous phase and the hydrocarbon-like interior of the membrane (Seelig, 1977;Ashcroft et al, 1981;Stubbs et al, 1985;Perochon et al, 1992;Slater et al, 1993;Venable et al, 1993;White and Wimley, 1994;Gawrisch et al, 1995) thus making it an ideal probe for monitoring red edge effects. Furthermore, previous electrophoretic measurements have shown that the NBD group in NBD-PE is uncharged at neutral pH in the membrane (Chattopadhyay and London, 1988).…”

“…This not only results in the anisotropic behavior of the constituent lipid molecules, but more importantly, the environment of a probe molecule becomes very much dependent on its precise localization in the membrane. While the center of the bilayer is nearly isotropic, the upper portion, only a few angstroms away toward the membrane surface, is highly ordered (Seelig, 1977;Ashcroft et al, 1981;Stubbs et al, 1985;Perochon et al, 1992;Slater et al, 1993;Venable et al, 1993;White and Wimley, 1994;Gawrisch et al, 1995). As a result, properties such as polarity, fluidity, segmental motion, ability to form hydrogen bonds and extent of solvent (water) penetration would vary in a depth-dependent manner in the membrane (Fig.…”

Effect of Ethanol and Osmotic Stress on Receptor Conformation

“…In addition, the physical properties of the surrounding phospholipid bilayer are known to modulate membrane function. Ethanol-induced changes in phospholipid hydrogen bonding have been observed to change acyl chain packing in pure lipid bilayers (5)(6)(7). Thus, the function of integral membrane receptors could be especially susceptible to the disruption of hydrogen-bonded water by ethanol.…”

Effect of ethanol perturbation on viscosity and permeability of an inner membrane in Bacillus subtilis spores

“…Water plays an extremely important role in the organization of the membrane bilayer and ethanol acts as a depressor of water activity. Slater et al, have shown that ethanol disrupts the role of the intra-membrane water and its inclusion leads to a decrease in a bilayer transition temperature [55].…”