MATHEMATICAL MODELING OF LIPID-MEDIATED COAGULATION REACTIONS

Blood coagulation is a network of biochemical reactions wherein dozens of proteins act collectively toinitiate a rapid clotting response. Coagulation reactions are lipid-surface dependent, and this dependenceis thought to help localize coagulation to the site of injury and enhance the association between reactants.Consideration of the lipid surface is critical in understanding the mechanisms of coagulation and bleedingdisorders. In this dissertation, we study the lipid-surface dependence of coagulation reactions through acombination of biochemical assays and mathematical modeling. We first develop a novel mathematicalframework for modeling enzyme reactions in the presence of lipid vesicles. This allowed for a mechanisticstudy of emicizumab, a treatment for hemophilia A. We build up to the two-arm interaction (figure 1) ina series of studies with distinct subsets of components. Overall, our work shows the importance of lipidbinding in coagulation reactions and offer insights into the design and optimization of future treatments.