A new mechanism for bistability in chemical reaction networks

Systems with counter-clockwise Input-Output dynamics were recently introduced in order to study convergence of positive feedback loops (possibly to many different equilibrium states). The paper shows how this notion can be used in order to perform bifurcation analysis and globally predict multistability of a closed-loop feedback interconnection just by using the knowledge of steady-state Input-Output responses of the systems. To illustrate the theory our method is then applied to a recently published model of MAPK cascade. Furthermore, a library of examples (mainly motivated by molecular biology) of systems which are guaranteed to enjoy the property is presented and discussed.