The Internal Model Principle for Biomolecular Control Theory

The well-known Internal Model Principle (IMP) is a cornerstone of modern control theory. It stipulates the necessary conditions for asymptotic robustness of disturbance-prone dynamical systems by asserting that such a system must embed a subsystem in a feedback loop, and this subsystem must be able to reduplicate the dynamic disturbance using only the regulated variable as the input. The insights provided by IMP can help in both designing suitable controllers and also in analysing the regulatory mechanisms in complex systems. So far the application of IMP in biology has been case-specific and ad hoc, primarily due to the lack of generic versions of the IMP for biomolecular reaction networks that model biological processes. In this short article we highlight the need for an IMP in biology and discuss a recently developed version of it for biomolecular networks that exhibit maximal Robust Perfect Adaptation (maxRPA) by being robust to the maximum number of disturbance sources.