Lipid Phase Transitions and Procoagulant Activity.

1. The relation between acyl chain fluidity of synthetic phosphatidylserine/phosphatidylcholine mixtures and their activity in the prothrombirtase complex has been investigated using differential scanning calorimetry and a one-stage prothrombinase assay. 2. Mixtures of dioleoylphosphatidylserine and dioleoylphosphatidylcholine which are liquid crystalline at physiological temperature proved to be considerably more active in coagulation than mixtures of dipalmitoylphosphatidylserine and dipalmitoylphosphatidylcholine which are in the gel phase, while this difference disappears completely upon addition of cholesterol. Varying the proportion of phosphatidylserine from 30 to 70 mol/100 mol has no significant influence on the coagulant behaviour. 3. The procoagulant activity of mixtures composed of dimyristoylphosphatidylserine and dipalmitoylphosphatidylcholine was compared with the phase diagram constructed from the calorie metric data. Going through the phase transition to the liquid state was accompanied by a sharp increase of clot-promoting activity. 4. The phospholipid concentration which exhibited maximal coagulant activity appeared to be strongly dependent on the miscibility properties of the lipids. Solid/solid immiscibility was observed both with mixtures of the two dimyristoyl compounds and the dipalmitoyl compounds, and a 5-10-fold increase in the lipid concentration required for maximal coagulant activity was observed below the phase transition. This shift was found 10 be absent with mixtures of the dioleoyl species or with dimyristoylphosphatidylserine-dipalmitoylphosphatidyicholine both of which showed essentially complete miscibility in both phases. [ABSTRACT FROM AUTHOR]

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