Multicellular PI control for gene regulation in microbial consortia

We describe two multicellular implementations of the classical P and PI feedback controllers for the regulation of gene expression in a target cell population. Specifically, we propose to distribute the proportional and integral actions over two different cellular populations in a microbial consortium comprising a third target population whose output needs to be regulated. By engineering communication among the different cellular populations via appropriate orthogonal quorum sensing molecules, we are able to close the feedback loop across the consortium. We derive analytical conditions on the biological parameters guaranteeing the regulation of the output of the target population and we validate the robustness and modularity of proposed control schemes via in silico experiments in BSim, a realistic agent-based simulator of bacterial populations.