BIFURCATION ANALYSIS IN APOPTOSIS (RECEPTOR CLUSTERING)

Abstract

Apoptosis is a designed cell death mechanism involved in biological processes. Apoptosis can either be activated by extrinsic pathway or by the intrinsic pathway. A major part of the external apoptosis pathway is the death receptor Fas which, on binding to its associated ligand FasL, they eventually form the death-inducing signaling complex. FasL promotes clustering for open Fas and activates open stable Fas, forming locally stable signaling platforms through neighborhood-induced receptor interactions. The model exhibits a bifurcation called hysteresis, providing an upstream mechanism for bistability and robustness to decide if the cell lives or dies. At low receptor concentrations, the bistability depends on three states of FasL. The irreversible bistability, representing a committed cell death decision, emerges at high receptor concentrations. Furthermore, the model suggests a mechanism by which cells may function as bistable life/death switches which are independent of their downstream dynamic components. This will be illustrated by simulations.