Integral control is commonly used in mechanical and electrical systems to ensure perfect adaptation. A proposed design of integral control for synthetic biological systems employs the sequestration of two biochemical controller species. The unbound amount of controller species captures the integral of the error between the current and the desired state of the system. However, implementing integral control inside bacterial cells using sequestration feedback has been challenging due to the controller molecules being degraded and diluted. Furthermore, integral control can only be achieved under stability conditions that not all sequestration feedback networks fulfill. In this work, we give guidelines for ensuring stability and good performance (small steady-state error) in sequestration feedback networks. Our guidelines provide simple tuning options to obtain a flexible and practical biological implementation of sequestration feedback control. Using tools and metrics from control theory, we pave the path for the systematic design of synthetic biological systems.

Design Guidelines For Sequestration Feedback Networks