Mathematical Biology Seminar Keshav Patel, University of Utah, Tuesday, Nov. 19, 2024 2:00pm in LCB 323 Understanding the Biochemical Determinants of Platelet Activation and Aggregation Abstract: Platelets are small anucleated cells responsible for initiating blood clotting in the event of injury. Platelets undergo many chemical and physical changes that allow them to form crosslinking bonds with other platelets and promote the activation of other nearby platelets. Disruption of these regulators can lead to stroke, bleeding, or other life-threatening disorders. In this talk, we will discuss two projects that examine regulation on separate spatial scales. First, we will discuss a detailed dynamical systems model of transient platelet activation by small nucleotide ADP. We utilize activation timecourse data from the Bergmeier Lab and platelet proteomics data to determine the essential proteins that modulate platelet integrin activation, highlighting potential therapeutic targets. We will follow by discussing a model of platelet aggregation in flowing blood. We particularly emphasize the polymeric protein Von Willebrand Factor (vWF), activated by mechanical forces typical in high shear rate blood flow. We show how dysregulation of vWF can lead to fast aggregate formation under low shear rate, leading to the occlusion of a blood vessel. Finally, we will discuss upcoming work on modeling vessel occlusion and embolism near vessels partially occluded by cholesterol.