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dc.contributor.authorLau, Wai-Hoeen_US
dc.contributor.authorWhite, Nathan J.en_US
dc.contributor.authorYeo, Tsin Wenen_US
dc.contributor.authorGruen, Russell L.en_US
dc.contributor.authorPervushin, Konstantinen_US
dc.identifier.citationLau, W., White, N. J., Yeo, T. W., Gruen, R. L. & Pervushin, K. (2021). Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods. Scientific Reports, 11(1), 15691-.
dc.description.abstractPlasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fibrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofibril lateral aggregation by disruption of AαC domain structures. However, experimental evidence explaining how HOCl oxidation impairs fibrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) to investigate the hypothesis that HOCl oxidation alters fibrinogen conformation and T₂ relaxation time of water protons in the fibrin gels. We have demonstrated that both HOCl oxidation of purified fibrinogen and addition of HOCl-oxidized fibrinogen to plasma fibrinogen solution disrupted lateral aggregation of protofibrils similarly to competitive inhibition of fibrin polymerization using a recombinant AαC fragment (AαC 419-502). DOSY NMR measurement of fibrinogen protons demonstrated that the diffusion coefficient of fibrinogen increased by 17.4%, suggesting the oxidized fibrinogen was more compact and fast motion in the prefibrillar state. 2D-NMR analysis reflected that water protons existed as bulk water (T₂) and intermediate water (T₂ᵢ) in the control plasma fibrin. Bulk water T₂ relaxation time was increased twofold and correlated positively with the level of HOCl oxidation. However, T₂ relaxation of the oxidized plasma fibrin gels was dominated by intermediate water. Oxidation induced thinner fibers, in which less water is released into the bulk and water fraction in the hydration shell was increased. We have confirmed that T₂ relaxation is affected by the self-assembly of fibers and stiffness of the plasma fibrin gel. We propose that water protons can serve as an NMR signature to probe oxidative rearrangement of the fibrin clot.en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.relation.ispartofScientific Reportsen_US
dc.rights© 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
dc.titleTracking oxidation-induced alterations in fibrin clot formation by NMR-based methodsen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsAlpha-C Fragmentsen_US
dc.description.acknowledgementWe would like to thank Dr. Mateusz Urbańczyk (University of Oulu, Finland) for providing 2D Inverse Laplace Transformation and compressed sensing MATLAB script. We acknowledged Bruker BioSpin GmbH for providing the NMR relaxometry and Dr. Marcio-Fernando Cobo (Bruker BioSpin GmbH, Rheinstetten, Germany) for invaluable discussions and technical assistance in the sample measurement and analysis. We also acknowledged Proteomic Core Facility of the Biological Research Center (BRC, NTU) for ESI-TOF MS analysis of the recombinant human αC construct. This work was funded by NTU Integrated Medical Biological and Environmental Life Sciences (NIMBELS), project reference: NIM/05/2016 (30/06/2017 to 29/12/2019).en_US
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