A comparative analysis of the bistability switch for platelet aggregation by logic ODE based dynamical modeling
01.08.2014
Mischnik M, Gambaryan S, Subramanian H, Geiger J, Schütz C, Timmer J, Dandekar T.
Mol Biosyst. 2014;10(8):2082-9.
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.
