Regulating population density through antithetic feedback control of cell growth

We present an analysis of a genetic feedback control strategy enabling engineered microorganisms to self-regulate their population density by leveraging a quorum sensing mechanism for the production of a growth inhibitor protein, whose activation is regulated by an embedded antithetic controller. Through mathematical modeling and steady-state analysis, we provide design guidelines to tune the reference parameter and critical rates—such as dilution and inhibitor production rates—to regulate density at steady state. We show that the proposed control architecture guarantees robust regulation of the cell density by validating its performance and robustness via realistic agent-based simulations in BSim, which accurately replicate the growth environment and capture key features like spatial constraints and cell growth.