A comparative analysis of the bistability switch for platelet aggregation by logic ODE based dynamical modeling

Abstract

A kinetic description of the fragile equilibrium in thrombozytes regulating blood flow would be an important basis for rational medical interventions. Challenges for such a model include regulation by a complex bistability switch that determines the transition from reversible to irreversible aggregation and sparse data on the kinetics. A so far scarcely applied technique is given by the derivation of ordinary differential equations from Boolean expressions, which are called logic ODEs. We employ a combination of light-scattering based thrombocyte aggregation data, western blot and calcium measurements to compare three different ODE approaches regarding their suitability to achieve a data-consistent model of the switch. Our analysis reveals the standardized qualitative dynamical system approach (SQUAD) to be a better choice than classical mass action formalisms. Furthermore, we analyze the dynamical properties of the platelet aggregation threshold as a basis for medical interventions such as novel platelet aggregation inhibitors.