(176ah) Modeling the Adhesive Behavior of Platelets during Coagulation

Platelets play a critical role in the mechanics and dynamics of blood clot behavior, but the exact contribution of individual platelets on the macro-scale mechanics of whole blood clots is not fully understood. As the first responders to a bleeding or thrombotic event, platelets release dense granules and undergo membrane surface conformational changes, resulting in the extension of adhesive mediators that facilitate the formation of small aggregate plugs found at the center of clots. The exposure to stiffer substrates increases the degree of platelet activation, and subsequently increases the adhesive capacity of platelets [1].

Since platelets are the building blocks of clots and thrombi, accurately capturing the mechanics and dynamics of platelet interactions is critical to building a meaningful multi-scale model of coagulation. We begin to bridge the trans-scale gap by first modeling the known cell-scale phenomena of activated platelets during coagulation. We have developed a discrete element method (DEM)-based model of platelet-platelet and platelet-fibrin interactions to capture the adhesive capacity that platelets acquire upon activation during the coagulation cascade. The adhesive properties observed by activated platelets in experimental isolated-platelet studies [2,3] can be modeled by implicitly including membrane-surface mediators of various lengths by defining concentric spheres about the in silico platelets, enabling our model to broadly capture the mechanics and dynamics of platelet-platelet and platelet-fibrin interactions.

Utilizing the same model for platelet-platelet and platelet-fibrin interactions that were implemented on the cell-scale, we can simulate assemblies composed of thousands of platelets and observe the emergent behavior as the trans-scale gap is traversed. Platelet concentrations and adhesive capacities were varied to investigate the effect of pathologies on overall clot strength, organization, and porosity. Future work involves
the extension of the model to include fibrin strands, red blood cells, and fluid plasma, resulting in a robust multi-scale model that captures the mechanics and dynamics of whole blood clots in silico.

[1] Qiu, Y., Barker, T.H., and Lam, W.A. (2014). Platelet mechanosensing of substrate stiffness during clot forma- tion. Proceedings of the National Academy of Sciences of the United States of America, 111(40), 14430–5.

[2] Lam, W.A., Huang, J., and Fletcher, D.A. (2011). Mechanics and dynamics of single platelets and implications for clot stiffening. Nature materials, 10(1), 61–6.

[3] Nguyen, T.H., Greinacher, A., and Delcea, M. (2016). Rupture forces among human blood platelets at different degrees of activation. Scientific Reports, 6(April), 25402.