Amidolytic, procoagulant, and activation-suppressing proteins produced by contact activation of blood factor XII in buffer solution

Avantika Golas, Chyi Huey Joshua Yeh, Christopher A. Siedlecki, Erwin A. Vogler

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The relative proportions of enzymes with amidolytic or procoagulant activity produced by contact activation of the blood zymogen factor XII (FXII, Hageman factor) in buffer solution depends on activator surface chemistry/energy. As a consequence, chromogenic assay of amidolytic activity (cleavage of amino acid bonds in s-2302 chromogen) does not correlate with the traditional plasma coagulation time assay for procoagulant activity (protease activity inducing clotting of blood plasma). Amidolytic activity did not vary significantly with activator particle surface energy, herein measured as water adhesion tension τo=γlvocosθa ; where γlvo is pure buffer interfacial tension and θ a is the advancing contact angle. By contrast, procoagulant activity varied as a parabolic-like function of τ o, high at both hydrophobic and hydrophilic extremes of activator surface energy and falling through a broad minimum within a 20<τ o<40 mJ/m 2 (55°<θ a < 75°) range, corroborating and expanding previously-published work. It is inferred from these functional assays that an unknown number of protein fragments are produced by contact activation of FXII (a.k.a. autoactivation) rather than just αFXIIa and βFXIIa as popularly believed. Autoactivation products produced by activator particles within the 20<τ o<40 mJ/m 2 (55°<θ a < 75°) surface-energy range suppresses production of procoagulant enzymes by activators selected from the hydrophobic or hydrophilic surface-energy extremes through as-yet unknown biophysical chemistry. Suppression proteins may be responsible for the experimentally-observed autoinhibition of the autoactivation reaction. This work shows that contact activation of the blood zymogen FXII is a complex surface-mediated reaction that produces a number of different kinds of protein fragments that can influence the hemocompatibility of cardiovascular biomaterials.

Original languageEnglish (US)
Pages (from-to)9747-9757
Number of pages11
JournalBiomaterials
Volume32
Issue number36
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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