Effects of Fibrinogen-Binding Tetrapeptides on Mechanical Properties of Fine Fibrin Clots

• Published in: Proceedings of the National Academy of Sciences - PNAS 1985-03, Vol.82 (5), p.1410-1413
• Main Authors: Bale, Marsha D., Muller, Michael F., Ferry, John D.
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Binding, Competitive; Biological and medical sciences; Blood Coagulation; Clotting; Diffusion; Elasticity; Ferries; Fibrin - metabolism; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; Ligation; Mechanical properties; Miscellaneous; Moduli of elasticity; Monomers; Nodules; Oligopeptides - metabolism; Protein Binding; Proteins; Shear modulus; Torque
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.5.1410

The tetrapeptides Gly-Pro-Arg-Pro and Gly-His-Arg-Pro, analogs of the amino termini of the α and β chains of fibrin monomer, respectively, were introduced by diffusion into fine unligated fibrin clots. Gly-Pro-Arg-Pro decreased the shear modulus of elasticity progressively and at a concentration of 5.8 mM the clot was eventually liquefied. The decrease in elastic modulus was accompanied by enormously enhanced viscoelastic creep under shear stress and irrecoverable deformation after removal of stress. However, the differential compliance (or modulus) for clots containing the tetrapeptide remained constant during creep and creep recovery, so the structure rearranged under stress without any permanent damage. Ligation with factor XIIIa and calcium largely eliminated these effects. From these changes in mechanical properties, it appears that Gly-Pro-Arg-Pro competes for binding sites, with consequent depolymerization. The tetrapeptide Gly-His-Arg-Pro at comparable concentrations decreased the modulus and increased the creep to a lesser degree; when combined with Gly-Pro-Arg-Pro it enhanced the effectiveness of the latter.