Department of Electrical Engineering and Information Technology, University of Naples Federico II, Via Claudio 21, 80125 Naples, Italy.
Department of Mathematics and Applications 'R. Caccioppoli', University of Naples Federico II, Via Cintia, Monte S. Angelo, 80126 Naples, Italy.
J R Soc Interface. 2022 Jul;19(192):20220335. doi: 10.1098/rsif.2022.0335. Epub 2022 Jul 13.
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.
我们解决了在单菌株微生物群落中调节和保持具有不同表型的细胞之间相对数量平衡的问题。我们提出了一种基于使用外部控制输入的策略，假设群落中的每个细胞都具有可逆的双稳态记忆机制。具体来说，我们提供了一个通用的分析框架来指导设计外部反馈控制策略，旨在平衡记忆被稳定在与不同细胞表型相关的两个平衡点之一的细胞的比例。我们证明了所提出的控制律的稳定性和鲁棒性，并通过遗传 toggle-switch 来验证它们，从而实现记忆元件。所提出的控制框架可用于允许不同群体的长期共存，具有工业和生物技术应用。作为一个代表性的例子，我们考虑了我们的控制策略的基于代理的现实实现，以在单菌株微生物群落中实现二聚体的合作生物生产。
