Abstract Number: LPB0110
Meeting: ISTH 2021 Congress
Theme: Fibrinogen, Fibrinolysis and Proteolysis » Fibrinogen and Factor XIII
Background: The fibrin network, which provides the scaffold for the blood clot, is a biopolymer with multiscale structural hierarchy leading to complex mechanical behaviour. As the last step of clot formation, activated coagulation factor XIII (FXIIIa) crosslinks the α- and γ-chains of fibrin, thus increasing clot stiffness.
Aims: To investigate how the presence/absence of γ-crosslinks alters fibrin mechanics in a novel murine model (FGG3X), we compared the stress-strain behaviour of wild type (WT) and γQ398N/Q399N/K406R fibrinogen (FGG3X), unable to undergo γ-γ crosslinking.
Methods: Clots of plasma-purified FGG3X or WT murine fibrinogen were made on a striated surface (0.5mg/ml fibrinogen, 0 or 10μg/ml rhFXIII-A2, 0.5U/ml thrombin, 5mM CaCl2). Individual fibrin fibers crossing between ledges were stretched with atomic force microscopy (AFM). Stress vs. strain curves were used for further analysis, where stress and strain were calculated from the lateral deflection and y-position of the cantilever, respectively.
Results: Compared with crosslinked FGG3X fibers, crosslinked WT fibers ruptured at significantly higher stress (2.2-fold, p<0.001), had 1.6-fold higher initial stiffness at low (<150%) strains (p<0.05), stiffened more (1.3-fold, p<0.01), reached a higher stiffness before rupture (2.8-fold, p<0.001) and had higher toughness (2.1-fold, p<0.01). Both uncrosslinked WT and FGG3X fibers showed similar parameters as the crosslinked FGG3X fibers.
Conclusions: In the presence of γ-γ crosslinks, individual fibrin fibers were less prone to rupture, as seen from the increased toughness, rupture stress and rupture stiffness of crosslinked WT fibers compared with crosslinked FGG3X fibers. Thus, when γ-chain crosslinks are present, fibers are much stronger and less prone to rupture. These findings may have important implications for clot fragmentation and thus thromboembolic diseases such as pulmonary embolism or cardioembolic stroke.
To cite this abstract in AMA style:
Feller T, Duval C, Connell SDA, Ariёns RAS. FXIIIa-mediated Fibrin γ-chain Crosslinks Are Critical for Fibrin Fiber Stiffness and Resistance to Rupture [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/fxiiia-mediated-fibrin-%ce%b3-chain-crosslinks-are-critical-for-fibrin-fiber-stiffness-and-resistance-to-rupture/. Accessed December 5, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/fxiiia-mediated-fibrin-%ce%b3-chain-crosslinks-are-critical-for-fibrin-fiber-stiffness-and-resistance-to-rupture/