Interaction of Zn2+ with phospholipid membranes Original Research Article

To characterize the specificity of zinc binding to phospholipid membranes in 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°C in the presence and absence of ZnCl2. Zinc forms a 2:1–1:1 complex with the lipid, and in particular with the negatively charged phosphate groups. Zn2+-bridges between neighboring lipid molecules stabilize the gel phase of the lipid relative to the liquid–crystalline state. 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 roughly 50% of the hydration shell. The ability of the Zn2+-bound phosphate groups to take up water is distinctly reduced, meaning that the headgroups have become less hydrophilic. The energetic cost (on the scale of Gibbs free energy) for completely dehydrating the lipid headgroups is decreased by approximately 10 kJ/mole in the presence of Zn2+. The interaction of phospholipid headgroups with Zn2+ is conveniently described by a hydrated zinc–phosphate complex the key energy contribution of which is more covalent than electrostatic in nature. Dehydration of phospholipid headgroups due to complexation with zinc cations is suggested to increase fusogenic potency of lipid membranes. Zinc appears to be one of the most potent divalent cation in inducing membrane fusion.