Cooperative reactions for designing robust biomolecular circuits exhibiting homeostatic behaviour

Chemical reaction networks (CRNs) provide an effective tool for designing robust synthetic biological feedback control circuits. Recently, we identified a two-state motif im plementing ultrasensitive feedback regulation functions that allow maintaining a homeostatic equilibrium, intrinsically embedded by the ultrasensitive characteristics itself, which is robust to environmental changes. Here, we devise a CRN that realizes the proposed two-state motif by exploiting cooperative reactions and show how increasing the level of cooperation yields adaptive, homeostatic equilibrium, robust to system uncertainties and possible disturbances.