Interaction of Zn2+ with phospholipid membranes

To characterize the specificity of zinc binding to phospholipid membranes i n terms of headgroup structure, hydration and phase behavior we studied the zwitterionic lipid 1-palmitoyl-2-oleoyl-phosphatidylcholine as a function of hydration at 30 degreesC in the presence and absence of ZnCl2. Zinc form s a 2:1-1:1 complex with the lipid, and in particular with the negatively c harged phosphate groups. Zn2+-bridges between neighboring lipid molecules s tabilize the gel phase of the lipid relative to the liquid-crystalline stat e. Upon Zn2+ binding the C-O-P-O-C- backbone of the lipid headgroup changes from a gauche/gauche into the trans/trans conformation and it loses roughl y 50% of the hydration shell. The ability of the Zn2+-bound phosphate group s to take up water is distinctly reduced, meaning that the headgroups have become less hydrophilic. The energetic cost ton the scale of Gibbs free ene rgy) for completely dehydrating the lipid headgroups is decreased by approx imately 10 kJ/mole in the presence of Zn2+. The interaction of phospholipid headgroups with Zn2+ is conveniently described by a hydrated zinc-phosphat e complex the key energy contribution of which is more covalent than electr ostatic in nature. Dehydration of phospholipid headgroups due to complexati on with zinc cations is suggested to increase fusogenic potency of lipid me mbranes. Zinc appears to be one of the most potent divalent cation in induc ing membrane fusion. (C) 2001 Elsevier Science B.V. All rights reserved.