Lipid Microenvironment Influences the Processivity of Adsorbed Fibrin(ogen): Enzymatic Processing and Adhesivity of the Bound Protein

Abstract

Abstract We assessed the processivity of fibrin(ogen) adsorbed to unmodified, and to lecithin-coated (160 A 2 · molecule -1 ), polystyrene-divinylbenzene beads. At saturation, lecithin-coated beads bind ∼22% less fibrinogen than do unmodified beads, a consequence of the protein being excluded from the area occupied by the hydrophilic head group of the lipid on the lecithin-coated surface. Despite this reduced capacity, lecithin-coated beads saturated with fibrinogen aggregate in the presence of thrombin at a rate and to an extent both greater than those of saturated unmodified beads. These differences cannot be due to inhibition of thrombin activity by the unmodified beads since liberation of fibrinopeptides A and B from both beads is quantitative. Whereas the action of thrombin on bound fibrinogen is indifferent to the lipid film, fibrinogenolysis is much more rapid and complete when fibrinogen is bound to the lecithin-coated surface than when it is bound to unmodified polystyrene-divinylbenzene. We attribute this to greater accessibility of plasmin-labile sites when the fibrinogen is coadsorbed with the phospholipid. Based on several results and observations, including thrombin-initiated aggregation of heads, and patterns of fibrinogenolysis and transamidation of adsorbed fibrin, we hypothesize that flexible, elongate fibrin(ogen) molecules bind to the hydrophobic regions of these surfaces in near end-on fashion, an orientation that appears to be preserved by lecithin. We propose further that the study of fibrin(ogen) on surfaces, lipid surfaces in particular, should provide information relevant to a host of physiologic/pathophysiologic processes where fibrin(ogen) deposition on surfaces occurs.