Background: Fibrin is the major mechanical component of blood clots and plays a critical role in 1) the formation of a strong, hemostatic seal to prevent bleeding and 2) the propensity for thrombotic embolization. While the viscoelastic mechanical properties of fibrin have been well studied, these properties are distinct from the ability of a material to resist rupture.

Aims: To determine the structure-function relationship of fibrin rupture.

Methods: To assess the dynamics of mechanical deformations/resistance to rupture, we performed tensile testing experiments on plasma blood clots with a single edge crack (Figure 1)  and correlated with ultrastructural studies (Figure 2). We developed a Fluctuating Spring model, which maps the changes in fiber alignment, stretching of the elastic network, and sequential rupture of coupled fibrin fibers with cooperativity on the strain-scale into a theoretical framework.

Experimental stress-strain analysis of the dynamics of deformation and rupture of a plasma clot with single-edge crack.
Scanning and transmission electron microscopy of plasma clots

Results: Through examination of experimental stress-strain curves and the fibrin ultrastructure, we determined that fibrin undergoes three distinct deformation regimes during the rupture process (Figure 1). We show that for fibrin gels formed under these conditions, the critical strain is 34–45% and the critical stress is 1.5–22 kPa. Our theoretical framework reveals that the presence of a crack or defect in the fibrin network renders them more stochastic. We show that the free energy associated with the fiber deformation and rupture is inversely related to the crack length; therefore, increasing crack length makes network rupture more spontaneous. By contrast, inter-fiber connectivity reinforces the fiber network, making rupture less likely to occur. Microscopy and theoretical results reveal that the fibrin network forms multifiber threads during the extension process; when strain exceeds the limits of the thread extensibility, the fibrin begins to rupture cooperatively.

Conclusions: The results obtained provide a fundamental understanding of blood clot breakage that underlies thrombotic embolization.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/strength-and-deformability-of-fibrin-clots-biomechanics-thermodynamics-and-mechanisms-of-rupture/