Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods

Abstract Plasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure hypochlorous acid (HOCl) increased methionine oxidation in severely injured trauma patients. Molecular dynamics suggests that poses a mechanistic link between oxidative stress through protofibril lateral aggregation disruption AαC domain structures. However, experimental evidence explaining how HOCl impairs structure function has not been demonstrated. utilized studies two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) investigate the hypothesis alters conformation T 2 relaxation time water protons gels. demonstrated both purified addition HOCl-oxidized plasma solution disrupted protofibrils similarly competitive inhibition using recombinant fragment (AαC 419–502). DOSY NMR measurement diffusion coefficient 17.4%, suggesting oxidized was more compact fast motion prefibrillar state. 2D-NMR analysis reflected existed as bulk (T ) intermediate 2i control fibrin. Bulk twofold correlated positively with level oxidation. gels dominated water. Oxidation induced thinner fibers, which less released into fraction hydration shell increased. confirmed affected self-assembly fibers stiffness gel. propose can serve signature probe rearrangement clot.