Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load

Britton, Samuel; Ким, Олег; Pancaldi, Francesco; Xu, Zhiliang; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark

doi:10.1016/j.actbio.2019.05.068

Cited by 25 publications

(23 citation statements)

References 65 publications

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“…However, in our experiments we observe fully intact fibers bundling with other intact fibers due to fiber reorientation during the tension redistribution that arises from individual fiber cleavage events. The bundling of fibers is mostly permanent, which is consistent with other studies of fiber cohesion, which have shown that a large amount of force is required to pull fibers apart that are stuck together at a junction [27,35,36]. Intact fiber bundling is a novel mechanism by which fibers are cleared during lysis, to our knowledge.…”

Section: Discussionsupporting

confidence: 89%

Inherent fibrin fiber tension propels mechanisms of network clearance during fibrinolysis

et al. 2020

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Proper wound healing necessitates both coagulation (the formation of a blood clot) and fibrinolysis (the dissolution of a blood clot). A thrombus resistant to clot dissolution can obstruct blood flow, leading to vascular pathologies. This study seeks to understand the mechanisms by which individual fibrin fibers, the main structural component of blood clots, are cleared from a local volume during fibrinolysis. We observed 2-D fibrin networks during lysis by plasmin, recording the clearance of each individual fiber. We found that, in addition to transverse cleavage of fibers, there were multiple other pathways by which clot dissolution occurred, including fiber bundling, buckling, and collapsing. These processes are all influenced by concentration of plasmin utilized in lysis. The network fiber density influenced the kinetics and distribution of these pathways. Individual cleavage events often resulted in large morphological changes in network structure, suggesting that the inherent tension in fibers played a role in fiber clearance. Using images before and after a cleavage event to measure fiber lengths, we estimated that fibers are strained ~23% beyond their equilibrium length during polymerization. To understand the role of fiber tension in fibrinolysis we modeled network clearance under differing amounts of fiber polymerized strain (prestrain). The comparison of experimental and model data indicated that fibrin tension enables 35% more network clearance due to network rearrangements after individual cleavage events than would occur if fibers polymerized in a non-tensed state. Our results highlight many characteristics and mechanisms of fibrin breakdown, which have implications on future fibrin studies, our understanding of the fibrinolytic process, and the development of thrombolytic therapies.

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Section: Discussionsupporting

confidence: 89%

Inherent fibrin fiber tension propels mechanisms of network clearance during fibrinolysis

et al. 2020

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“…, 2019 ). Also, the formation of new cohesive cross-links between fibers was recently described in experiments of stretched fibrin gels ( Britton et al. , 2019 ).…”

Section: Discussionmentioning

confidence: 81%

Long-range mechanical coupling of cells in 3D fibrin gels

Natan

Koren

Shelah

et al. 2020

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“…An example of such a mechanism in synthetic hydrogels is the transformation of polymer domains ( 15 ), which has a direct analog in fibrin as unfolding of individual fibrin monomers ( 10 ), and stretching of long flexible αC-polymers, connecting protofibrils within a fibrin fiber ( 11 ). Similarly, the formation and breakage of adhesive interactions in fibrin that leads to reversible bundling of fibers upon clot deformation ( 16 ) (rather than irreversible covalent crosslinking) is another toughening mechanism ( 15 ). Yet, another toughening mechanism that is absent in isochorically deforming hydrogels is dissipation due to motion of fluid (volume decrease) in fibrin gels ( 17 ), although its contribution is small in the gels tested here because of the large pore sizes and low stretching rates.…”

Section: Discussionmentioning

confidence: 99%

Rupture of blood clots: Mechanics and pathophysiology

et al. 2020

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Fibrin is the three-dimensional mechanical scaffold of protective blood clots that stop bleeding and pathological thrombi that obstruct blood vessels. Fibrin must be mechanically tough to withstand rupture, after which life-threatening pieces (thrombotic emboli) are carried downstream by blood flow. Despite multiple studies on fibrin viscoelasticity, mechanisms of fibrin rupture remain unknown. Here, we examined mechanically and structurally the strain-driven rupture of human blood plasma–derived fibrin clots where clotting was triggered with tissue factor. Toughness, i.e., resistance to rupture, quantified by the critical energy release rate (a measure of the propensity for clot embolization) of physiologically relevant fibrin gels was determined to be 7.6 ± 0.45 J/m2. Finite element (FE) simulations using fibrin material models that account for forced protein unfolding independently supported this measured toughness and showed that breaking of fibers ahead the crack at a critical stretch is the mechanism of rupture of blood clots, including thrombotic embolization.

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Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load

Cited by 25 publications

References 65 publications

Inherent fibrin fiber tension propels mechanisms of network clearance during fibrinolysis

Inherent fibrin fiber tension propels mechanisms of network clearance during fibrinolysis

Long-range mechanical coupling of cells in 3D fibrin gels

Rupture of blood clots: Mechanics and pathophysiology

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