Controlling reversible cell differentiation for labor division in microbial consortia

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 to different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them in silico by means of a realistic agent-based implementation enabling cooperative bioproduction in microbial consortia. The proposed control framework may be used to allow long term coexistence of different populations, with both industrial and biotechnological applications.