Shear strengthens fibrin: the knob-hole interactions display “catch-slip” kinetics

R. I. Litvinov, J. W. Weisel
The polymerization of fibrin occurs primarily via intermolecular non-covalent binding between knobs ‘A’ exposed by cleavage of fibrinopeptides A in the Aα chains of fibrinogen and holes ‘a’ constitutively present in the γ chains [1]. We have previously investigated the interactions between knobs ‘A’ and holes ‘a’ at the single-molecule level and have found that they are strong and stable [2] with complex forced unbinding mechanisms [3]. The structural complexity and thermodynamics of these interactions must be reflected in the non-trivial dynamics of the mechanical response of the knob-hole bond to stress. By applying an original model system to quantify the mechanical dissociation of individual knob-hole complexes, we revealed an unusual strengthening of A:a knob-hole bonds in response to increasing pulling force, referred to as a “catch” bond.

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