THERMODYNAMICS OF MIXING OF PHOSPHATIDYLSERINE PHOSPHATIDYLCHOLINE FROM MEASUREMENTS OF HIGH-AFFINITY CALCIUM-BINDING

A simple model system is described that allows measurement of equilibrium Ca2+ binding to multilamellar vesicle mixtures of palmitoyloleoylphosphatidylserine (P,O-PS) and dimyristoleoylphosphatidylcholine (MO,MO-PC). The constraint of the chemical equilibrium among aqueous Ca2+, hydrated P,O-PS/MO,MO-PC, and Ca(PS)2, together with measurements of the Ca2+ concentration in equilibrium with defined PS/PC ratios, enables the determination of the thermodynamic activity of the lipids. The activity coefficient of dilute P,O-PS in PC is analyzed in terms of the partial molai free energy to transfer P,O-PS from an environment of PS to an environment of PC. This study of P,O-PS/MO,MO-PC, by comparison with the earlier study of P,O-PS/P,O-PC [Feigenson, G. W. (1989) Biochemistry 20, 1270-1278], reveals that the excess partial molai free energy to transfer P,O-PS from P,O-PS to P,O-PC is −0.7 kcal mol−1. This free energy change arises in part from the favorable transfer of the negatively charged phosphoserine headgroup from an environment of negative charges to an environment of zwitterions. The contribution of acyl chain mismatch to the partial molai free energy to transfer P,O-PS from P,O-PS to MO,MO-PC is found to be approximately +0.7 kcal mol−1. This value is much larger than that of the excess partial molai free energy of mixing in isotropic solutions of linear hydrocarbons that differ in chain length or unsaturation. © 1990, American Chemical Society. All rights reserved.