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Embedded control of cell growth using tunable genetic systems
Author(s) -
Fusco Virginia,
Salzano Davide,
Fiore Davide,
di Bernardo Mario
Publication year - 2023
Publication title -
international journal of robust and nonlinear control
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.361
H-Index - 106
eISSN - 1099-1239
pISSN - 1049-8923
DOI - 10.1002/rnc.5982
Subject(s) - robustness (evolution) , quorum sensing , flexibility (engineering) , population , computer science , control theory (sociology) , feedback control , in silico , control engineering , control (management) , engineering , mathematics , biology , artificial intelligence , biochemistry , statistics , genetics , demography , biofilm , sociology , bacteria , gene
We present an embedded feedback control strategy to regulate the density of a microbial population, that is, the number of cells into a given environment, allowing cells to self‐regulate their growth rate so as to reach a desired density at steady state. We consider a static culture condition, where cells are provided with a limited amount of space and nutrients. The control strategy is built using a tunable expression system (TES), which controls the production of a growth inhibitor protein, complemented with a quorum sensing mechanism for the sensing of the population density. We show via a simplified population‐level model that the TES endows the control system with additional flexibility by allowing the set‐point to be changed online. Finally, we validate the effectiveness of the proposed control strategy by means of realistic in silico experiments conducted in BSim, an agent‐based simulator explicitly designed to simulate bacterial populations, and we test the robustness of our design to disturbances and parameters' variations due, for instance, to cell‐to‐cell variability.