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

• Published in: Nanomedicine 2018-04, Vol.14 (3), p.909-918
• Main Authors: Guedes, Ana Filipa, Carvalho, Filomena A., Domingues, Marco M., Macrae, Fraser L., McPherson, Helen R., Santos, Nuno C., Ariёns, Robert A.S.
• Format: Article
• Language: English
• Subjects: Atomic force microscopy; Blood Coagulation; Cell Adhesion; Erythrocytes - metabolism; Erythrocytes - ultrastructure; Fibrin - metabolism; Fibrin - ultrastructure; Fibrin clot; Fibrinogen - metabolism; Fibrinogen - ultrastructure; Fibrinogens, Abnormal - metabolism; Fibrinogens, Abnormal - ultrastructure; Hemostatics; Humans; Magnetic tweezers; Microscopy, Atomic Force; Microscopy, Electron, Scanning; γ’ fibrinogen
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.01.006

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. Comparison of the interaction between red blood cells (RBCs) and γAγA or γAγ’ fibrinogen. Schematic representation of the adhesion forces between two RBCs in the presence of γAγ’ fibrinogen, which affects clot properties and function. Changes on fibrin network structure, decreased fiber diameter, increased fibrinolysis and decreased permeability by γAγ’ fibrinogen-RBC interactions were encountered. The nanotechnology-based approach was essential to understand that the RBCs interact differently with clots made with γ’ chain fibrinogen splice variant instead of the common variant, γA. This may explain some of the cardiovascular clinical associations that have been reported for γ’ fibrinogen. [Display omitted]