Multicellular PID control for robust regulation of biological processes.

Abstract

This article presents the first implementation of a proportional-integral-derivative (PID) biomolecular controller within a consortium of different cell populations, aimed at robust regulation of biological processes. By leveraging the modularity and cooperative dynamics of multiple engineered cell populations, we develop a comprehensive <i>in silico</i> analysis of the performance and robustness of P, PD, PI and PID control architectures. Our theoretical findings, validated through <i>in silico</i> experiments using the BSim agent-based simulation platform for bacterial populations, demonstrate the robustness and effectiveness of our multicellular PID control strategy. This innovative approach addresses critical limitations in current control methods, offering significant potential for applications in metabolic engineering, therapeutic contexts and industrial biotechnology. Future work will focus on experimental validation <i>in vivo</i> and further refinement of the control models.