A Mathematical Model of Receptor-Mediated Apoptosis: Dying to Know Why FasL is a Trimer

Abstract

The scientific importance of understanding programmed cell death is undeniable; however, the complexity of death signal propagation and the formerly incomplete knowledge of apoptotic pathways has left this topic virtually untouched by mathematical modeling. In this paper, we use a mechanistic approach to frame the current understanding of receptor-mediated apoptosis with an immediate goal of isolating the role receptor trimerization plays in this process. Analysis and simulation suggest that if the death signal is to be successful at low-receptor, high-ligand concentration, Fas trimerization is unlikely to be the driving force in the signal propagation. However at high-receptor and low-ligand concentrations, the mathematical model illustrates how the ability of FasL to cluster three Fas receptors can be crucially important for downstream events that propagate the apoptotic signal.