Comparison of the abilities of synthetic and platelet-derived membranes to enhance thrombin formation

Abstract

The relative abilities of platelet-derived membranes and synthetic phospholipid vesicles to enhance the prothrombinase-catalyzed conversion of prothrombin to thrombin have been determined. For each type of membrane, the maximum amount of thrombin formed as a function of amount of available lipid was measured using a chromogenic substrate assay. The lipid concentration at which the amount of thrombin formed began to exceed that formed in the absence of lipid (critical phospholipid concentration) was used to compare the surfaces' abilities to support thrombin formation. For platelet-derived membranes and for equimolar, charged-lipid/phosphatidylcholine (PC) vesicles, the critical concentrations increased in the following order: platelet-derived membranes approximately equal to phosphatidylserine (PS) approximately equal to phosphatidic acid (PA) less than monomethyl PA and monoethyl PA much less than phosphatidylinositol and phosphatidylglycerol. For mixed anionic/neutral lipid vesicles above their phase transitions, measured critical concentrations were relatively insensitive to changes in lipid acyl chains, the neutral lipid component, and membrane curvature but were sensitive to changes in the anionic lipid content of the mixtures. Comparison of these data suggested that equimolar PS/PC and PA/PC vesicles can emulate reasonably well the thrombin-generating ability of platelet-derived membranes.