Ratiometric control of cell phenotypes in monostrain microbial consortia.

Davide Salzano, Davide Fiore, Mario di Bernardo
Author Information
  1. Davide Salzano: Department of Electrical Engineering and Information Technology, University of Naples Federico II, Via Claudio 21, 80125 Naples, Italy. ORCID
  2. Davide Fiore: Department of Mathematics and Applications 'R. Caccioppoli', University of Naples Federico II, Via Cintia, Monte S. Angelo, 80126 Naples, Italy. ORCID
  3. Mario di Bernardo: Department of Electrical Engineering and Information Technology, University of Naples Federico II, Via Claudio 21, 80125 Naples, Italy. ORCID

Abstract

We address the problem of regulating and keeping at a desired balance the relative numbers between cells exhibiting a different phenotype within a monostrain microbial consortium. We propose a strategy based on the use of external control inputs, assuming each cell in the community is endowed with a reversible, bistable memory mechanism. Specifically, we provide a general analytical framework to guide the design of external feedback control strategies aimed at balancing the ratio between cells whose memory is stabilized at either one of two equilibria associated with different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them , implementing the memory element via a genetic toggle-switch. The proposed control framework may be used to allow long-term coexistence of different populations, with both industrial and biotechnological applications. As a representative example, we consider the realistic agent-based implementation of our control strategy to enable cooperative bioproduction of a dimer in a monostrain microbial consortium.

Keywords

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MeSH Term

Biotechnology
Microbial Consortia
Phenotype