title: Surface-dependent fibrinopeptide A accessibility to thrombin.
abstract: Fibrinogen adsorption and more recently fibrin formation at interfaces has been reported to depend on surface properties of the underlying substrate. To provide insight into the surface-dependent mechanism of fibrinopeptide A (FpA) release and fibrin formation, the accessibility and susceptibility of FpA to thrombin-catalyzed fibrinopeptide cleavage were examined using polyclonal anti-FpA IgG binding and surface plasmon resonance (SPR). The amount of accessible FpA on adsorbed fibrinogen was significantly influenced by surface properties of the underlying substrate (methyl- and carboxyl-terminated self-assembled monolayers). Roughly 2.7 times more FpA was available on fibrinogen adsorbed at the hydrophobic vs. negatively charged surface. Upon exposure of adsorbed fibrinogen to thrombin, 100% of the available FpA was enzymatically cleaved at both surfaces, indicating that the extent of FpA release and fibrin formation is a function of the surface-dependent FpA availability. The results presented herein suggest negatively charged surfaces impair FpA accessibility, and therefore lead to reduced FpA release and subsequent fibrin formation. As such, negatively charged surfaces may be useful in minimizing surface-induced thrombosis initiated via fibrin formation thereby aiding in the development of more biocompatible blood-contacting devices.
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Carri B
authors.initials: CB
authors.lastname: Geer
authors.forename: Ioana A
authors.initials: IA
authors.lastname: Rus
authors.forename: Susan T
authors.initials: ST
authors.lastname: Lord
authors.forename: Mark H
authors.initials: MH
authors.lastname: Schoenfisch
mesh_terms: D000327:Adsorption; D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry*; D005344:Fibrinopeptide A / Q000737:chemistry*; D008422:Materials Testing; D011485:Protein Binding; D013499:Surface Properties; D013917:Thrombin / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D001672:Biocompatible Materials; D005344:Fibrinopeptide A; D013917:Thrombin