A Mechanism of Divalent Ion-induced Phosphatidylserine Membrane Fusion

A mechanism for the divalent cation-induced membrane fusion of phosphatidylserine membranes is proposed. Fusion was followed by the Tb/DPA (dipicolinic acid) assay, monitoring the fluorescent intensity for mixing of the internal aqueous contents of unilamellar lipid vesicles, and the threshold concentrations required for various divalent cations to induce membrane fusion were determined from the fluorescence spectrum of the lipid vesicle suspension with respect to various concentrations of divalent ions. Also, the surface tension of monolayers made of the same lipids as used in the fusion experiments was measured with respect to the variation of divalent cation concentrations. The surface tension increase in the monolayer, induced by changing divalent ion concentrations from zero to a concentration which corresponded to its threshold concentration to induce vesicle membrane fusion, was the same (approx. 8 dyn/cm) for all divalent ions used. From these experimental data and theory concerning ion binding to the membrane, it is deduced that the main cause of divalent cation-induced membrane fusion of phosphatidylserine membranes is the degree of increased hydrophobicity (surface tension increase) of the membrane surface, which results from the binding of cations to acidic phospholipid membrane surfaces. Some discussion on the molecular mechanism of phospholipid membrane fusion is given.