Martinelli, Vittoria (University of Naples Federico II), Fiore, Davide (University of Naples Federico II), Salzano, Davide (University of Naples Federico II), Di Bernardo, Mario (University Of Naples Federico II)

Root Contours Guided Design of a Multicellular PID Controller

Scheduled for presentation during the Regular Session "Genetic and evolutionary computation" (WeAD), Wednesday, June 11, 2025, 12:10−12:30, Room C

33rd Mediterranean Conference on Control and Automation, June 10-13, 2025, Tangier, Morocco

This information is tentative and subject to change. Compiled on May 9, 2025

Abstract

Ensuring a stable and robust phenotype expression is a key challenge for the correct operation of synthetically engineered cells, and feedback has been highlighted as a key mechanism to achieve this goal. Biomolecular PID controllers have been extensively leveraged at a single cell level to regulate gene expression. However, single-cell architectures suffer from limited modularity and might pose a significant challenge for their in vivo implementation due to high metabolic load and possible incompatible reactions. To overcome these limitations, it has been proposed to distribute the control actions over different cell populations realizing a multicellular feedback control architecture. In this paper we provide design guidelines derived by means of the root contours method to tune the control gains of a multicellular PID controller. We then validate performance, robustness and modularity of the multicellular PID controller through in silico simulations in BSim.