Embedding ultrasensitivity via cooperation in biomolecular circuit design: a framework for robust adaptation

Chemical reaction networks (CRNs) serve as powerful frameworks for designing robust synthetic biological feedback control circuits. Recently, we identified a two-state motif that employs ultrasensitive feedback regulation to maintain a homeostatic equilibrium, inherently robust to environmental fluctuations. In this work, we construct a CRN that embeds the proposed two-state motif through cooperative reactions and demonstrate that increasing the level of cooperation enhances adaptive homeostasis, ensuring robustness against system uncertainties and external disturbances.