Sensing adhesion forces between erythrocytes and γ’ fibrinogen, modulating fibrin clot architecture and function

Guedes, Ana Filipa; Carvalho, Filomena Almeida; Domingues, Marco; Macrae, Fraser L.; McPherson, Helen R.; Santos, Nuno C.; Ariёns, Robert A.S.

http://hdl.handle.net/10451/37861

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Authors

Guedes, Ana Filipa

Carvalho, Filomena Almeida

Abstract(s)

Plasma fibrinogen includes an alternatively spliced γ-chain variant (γ'), which mainly exists as a heterodimer (γAγ') and has been associated with thrombosis. We tested γAγ' fibrinogen-red blood cells (RBCs) interaction using atomic force microscopy-based force spectroscopy, magnetic tweezers, fibrin clot permeability, scanning electron microscopy and laser scanning confocal microscopy. Data reveal higher work necessary for RBC-RBC detachment in the presence of γAγ' rather than γAγA fibrinogen. γAγ' fibrinogen-RBCs interaction is followed by changes in fibrin network structure, which forms an heterogeneous clot structure with areas of denser and highly branched fibrin fibers. The presence of RBCs also increased the stiffness of γAγ' fibrin clots, which are less permeable and more resistant to lysis than γAγA clots. The modifications on clots promoted by RBCs-γAγ' fibrinogen interaction could alter the risk of thrombotic disorders.