FEEDBACK-INDUCED COMPLEX DYNAMICS IN A TWO-COMPONENT REGULATORY CIRCUIT

Abstract

Coupled positive and negative feedback loops form an essential building block of cellular signaling pathways, but the dynamics of such a system remain to be fully explored. Here, we systematically analyze a two-component circuit with interlinked positive and negative feedback loops, focusing on feedback-induced dynamics and their mechanisms. We show that feedbacks can induce monostability, oscillation, and excitability as well as the coexistence of two attractors (including that of two different stable steady states (called Type-I bistability) and that of both a stable steady state and a stable limit cycle (called Type-II bistability)). In particular for Type-II bistability, we find that feedback-controlled molecular noise can induce stochastic switching between two different attractors, and that the first passage time between them exhibits a multi-peak distribution. These investigations provide insights for understanding the biological functions of coupled positive and negative feedback circuits from the viewpoint of dynamics.