Strength, deformability and toughness of uncrosslinked fibrin fibers from theoretical reconstruction of stress-strain curves

Structural mechanisms underlying the mechanical properties of fibrin fibers are elusive. We combined tensile testing of uncrosslinked fibrin polymers in vitro and in silico to explore their material properties. The experimental stress (sigma) - strain (epsilon) curves for fibrin fibers are characterized by elastic deformations with a weaker elastic response for epsilon<160% due to unraveling of alpha C. tethers and straightening of fibrin protofibrils, and a stronger response for epsilon>160% owing to unfolding of the coiled coils and gamma nodules in fibrin monomers. Fiber rupture for strains epsilon>212% is due to dissociation of the knob-hole bonds and rupture of D:D interfaces. We developed the Fluctuating Bilinear Spring model to interpret the sigma - epsilon profiles in terms of the free energy for protofibril alignment Delta G(0) = 10.1-11.5 k(B)T, Young's moduli for protofibril alignment Y-u = 1.9-3.2 MPa and stretching Y-a = 5.7-9.7 MPa, strain scale (epsilon) over tilde 12-40% for fiber rupture, and protofibril cooperativity m = 3.6-8. We applied the model to characterize the fiber strength sigma(cr) approximate to 12-13 MPa, deformability epsilon(cr) approximate to 222%, and rupture toughness U approximate to 9 MJ/m(3), and to resolve thermodynamic state functions, 96.9 GJ/mol entropy change for protofibril alignment (at room temperature) and 113.6 GJ/mol enthalpy change for protofibril stretching, which add up to 210.5 GJ/mol free-energy change. Fiber elongation is associated with protofibril dehydration and sliding mechanism to create an ordered protofibril array. Fibrin fibers behave like a hydrogel; protofibril dehydration and water expulsion account for similar to 94-98% of the total free-energy changes for fiber elongation and rupture. Statement of significance Structural mechanisms underlying the mechanical properties of fibrin fibers, major components of blood clots and obstructive thrombi, are elusive. We performed tensile testing of uncrosslinked fibrin polymers in vitro and in silico to explore their material properties. Fluctuating Bilinear Spring theory was developed to interpret the stress-strain profiles in terms of the energy for protofibril alignment, elastic moduli for protofibril alignment and stretching, and strain scale for fiber rupture, and to probe the limits of fiber strength, extensibility and toughness. Fibrin fibers behave like a hydrogel. Fiber elongation is defined by the protofibril dehydration and sliding. Structural rearrangements in water matrix control fiber elasticity. These results contribute to fundamental understanding of blood clot breakage that underlies thrombotic embolization. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

The structural mechanisms of fibrin fiber mechanical properties are complex, involving elastic deformations, unraveling of alpha C. tethers, unfolding of coiled coils, and rupture due to dissociation of bonds. The Fluctuating Bilinear Spring model was developed to interpret stress-strain profiles and characterize fiber strength, extensibility, and toughness. Fiber elongation is related to protofibril dehydration and sliding, contributing to a better understanding of blood clot breakage.