Interactions of La 3+ with phosphatidylserine vesicles Binding, phase transition, leakage, 31P-NMR and fusion

Abstract

The interaction of La 3+ with phosphatidylserine vesicles is studied by differential scanning calorimetry, 140La binding, 31P-NMR chemical shifts and relaxation rates, carboxyfluorescein and [ 14C]sucrose release, X-ray diffraction and freeze-fracture electron microscopy. In the presence of La 3+ concentrations above 1 mM and an incubation temperature of 38°C, i.e., at the phase transition temperature of the complex La/phosphatidylserine, the binding ratio of La/lipid exceeds a 1 3 ratio, reaching saturation at a 1 2 ratio. Analysis, employing a modified Gouy-Chapman equation, indicates a significant increase in the intrinsic binding constant of La/phosphatidylserine when the La 3+ concentration exceeds the threshold concentration for leakage. The analysis illustrates that at the molecular level the binding of La 3+ can be comparable to or even weaker than that of Ca 2+, but that even when present at smaller concentrations La 3+ competes with and partially displaces Ca 2+ from membranes or other negatively charged surfaces. The results suggest that the sequence La 3+>Ca 2+>Mg 2+ reflects both the binding strength of these cations to phosphatidylserine as well as their ability to induce leakage, enhancement of 31P spin-lattice relaxation rates, fusion and other structural changes. The leakage, fusion, and other structural changes are more pronounced at the phase transition temperature of the La/lipid complex.