Phospholipid composition influences the binding of multimerin 1 and factor V/Va to the platelet membrane and modulates thrombin generation in plasma

Abstract

Multimerin 1 (MMRN1) binds coagulation factor V (FV) and its activated form (Va) with high affinity. Both proteins bind to activated platelets and to platelet-like membranes containing phosphatidylserine (PS) and phosphatidylehtanolamine (PE). The attenuation of FV dependent plasma thrombin generation in vitro, and the activation dependent binding of MMRN1 to platelets, led us to evaluate MMRN1 and FV/Va binding to membranes of various lipid compositions. Binding was evaluated by phospholipid binding ELISA, and surface plasmon resonance. Like FVa, MMRN1-lipid binding was enhanced by increasing PS content of PS:PC membranes, and by increasing PE and cholesterol content of low PS membranes. While FV binding was enhanced by increasing PE content, significant binding occurred without PE, and to pure PC. Lipid mixtures that were optimal for MMRN1 and FVa binding also enhanced thrombin generation in plasma (without MMRN1) as measured by modified calibrated automated thrombograms. The data suggest that activation-induced changes in the platelet membrane lipid distribution, alter MMRN1 and FVa binding, and influence the ability of MMRN1 to modulate FV/Va function in coagulation. Supported by CIHR and HSFO grants