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LCN2 Seminar: Multi-scale models of fibrin networks

vrijdag 27 september 2019
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden
Science club

34th LCN2 seminar

Speaker: Mark Alber (University of California Riverside, USA)

Title: Multi-scale models of fibrin networks

Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). Fibrin is a viscoelastic proteinaceous polymer that determines the deformability and integrity of blood clots and fibrin-based biomaterials in response to biomechanical forces. In this talk, a previously unnoticed structural mechanism of fibrin clots’ mechanical response to external tensile loads is tested using high-resolution confocal microscopy and recently developed three-dimensional computational model of fibrin network [1]. This mechanism, underlying local strain-stiffening of individual fibers as well as global stiffening of the entire network, is based on novel nascent cohesive pairwise interactions between individual fibers (crisscrossing) in fibrin networks formed under tensile load. Existence of fiber-fiber crisscrossings of reoriented fibers was confirmed using 3D imaging of experimentally obtained stretched fibrin clots.

The computational model enabled us to study structural details and quantify mechanical effects of the fiber-fiber cohesive crisscrossing during stretching of fibrin gels at various spatial scales. The contribution of the fiber-fiber cohesive contacts to the elasticity of stretched fibrin networks was characterized by changes in individual fiber stiffness, the length, width, and alignment of fibers, as well as connectivity and density of the entire network. The results show that the nascent cohesive crisscrossing of fibers in stretched fibrin networks comprise an underappreciated important structural mechanism underlying the mechanical response of fibrin to (patho)physiological stresses that determine the course and outcomes of thrombotic and hemostatic disorders, such as heart attack and ischemic stroke. Role of platelets-fibrin network mechanical interactions in determining shape of a contracting clot will be also discussed and quantified using analysis of experimental data [2]. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions.

1. Samuel Britton, Oleg Kim, Francesco Pancaldi, Zhiliang Xu, Rustem I. Litvinov, John W.Weisel, Mark Alber [2019], Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load, Acta Biomaterialia 94 (2019) 514–523.
2. Oleg V. Kim, Rustem I. Litvinov, Mark S. Alber & John W. Weisel, Quantitative structural mechanobiology of platelet driven blood clot contraction, Nature Communications 8: 9 (2017) 1274.

About the LCN2 seminar

This talk is part of a series of seminars organized within an ongoing scientific initiative called the "Leiden Complex Networks Network" (LCN2), which brings together scientists with a common interest in both theoretical models and empirical analyses of complex networks and random graphs. The LCN2 community shares the approach of using networks for describing real-world complex systems and aims at developing related analytical and numerical methods, while also being open to other research approaches for studying complex systems. The talks are designed for a broad audience, allowing for constructive exchanges of ideas between scientists from different disciplines. During and after the talk, drinks and snacks are provided.

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