Modeling mechanics and dynamics of blood clot contraction
Staff - Faculty of Informatics
Date: 8 September 2023 / 13:00 - 14:00
D5.01, Sector D, East Campus
Speaker: Dr. Alexander Alexeev, George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology
Abstract: Contraction of blood clots plays an important role in blood clotting, a natural physiological process that restores hemostasis and regulates thrombosis in the body. Upon vascular injury, a cascade of signaling events culminate in the formation of a soft plug of cells and fibrin fibers attaching to wound edges. Platelets become activated and undergo acto-myosin-based contraction with nascent fibrin fibers to shrink the overall clot size, modify clot structure, and mechanically stabilize the clot. We develop an experimentally informed, physics-based mesoscale computational model of the interactions among platelets, fibrin fibers, RBCs, and plasma fluid to connect the physiological blood clot forming conditions and the properties of contracted blood clots. Our work is the first to characterize and quantify the dynamic processes taking place in contracting clots at both the microscopic cell level and the macroscopic bulk clot level. Our model predicts the contraction process for clots at different physiological conditions, allowing us to quantify the effects of various factors on clot contraction, such as clot size, platelet and fibrinogen concentrations, platelet force, platelet heterogeneity, presence of RBCs, RBC biomechanics, and flow. The simulations provide the mechanistic understanding of the mechanics by which single platelet forces are related to the forces generated by macroscopic clots, and yield a relationship between single platelet force and the clot force. Our simulations reveal that platelets utilize a new emergent behavior, triggered by the heterogeneity in the timing of platelet activation, to enhance volumetric material contraction and to magnify contractile forces. The simulations show that RBC retention and compaction in thrombi can be solely a result of mechanical contraction of fibrin mesh due to platelet activity. The retention of RBCs inside clots hinders clot contraction and reduces clot contractility, whereas the expulsion of RBCs at the clot outer surface results in the development of a dense fibrin shell commonly observed in experiments.
Biography: Dr. Alexeev is a Professor in the Woodruff School of Mechanical Engineering at Georgia Institute of Technology. He received his Ph.D. from the Technion in Israel. Before joining Georgia Tech, he was a postdoctoral researcher at the Technical University of Darmstadt in Germany and the University of Pittsburgh. Dr. Alexeev conducts research in computational fluid dynamics, soft matter, and mesoscale modeling using high-performance computing. His research is motivated by solving practical and fundamental problems at the intersection of engineering, medicine, and biology.
Host: Prof. Igor Pivkin