Abstract :
[en] Isogenic cell populations possess the ability to cope with unpredictable environmental changes by expressing a wide range of phenotypes. Although this adaptation is advantageous in natural settings, it is often undesirable in applications such as bioproduction, synthetic biology, and biomedicine, as it hinders control over the cellular population behavior. However, there is limited knowledge regarding the diversification profiles exhibited by cell populations.
In our study, we focused our analysis on various phenotypes in continuous culture, including carbon source utilization and stress response across multiple model organisms such as bacteria and yeast. Remarkably, our findings revealed a connection between the diversification and the associated fitness cost of cell switching.
To isolate the influence of the switching cost on population dynamics, we developed a stochastic model that successfully replicated the experimentally observed dynamics. This modeling approach led us to identify three distinct diversification regimes: constrained (at a low switching cost), dispersed (at medium and high switching costs), and bursty (for very high switching costs).
Furthermore, we utilized a cell-machine interface, referred to as the Segregostat, to demonstrate the feasibility of exerting different levels of control over these diversification regimes. This is particularly relevant in industrial settings where production load, i.e., fitness cost, exists. By employing this framework, we aim to improve the induction robustness of a system well known for its high production load, E. coli BL21 T7, thereby enhancing control and efficiency in bioproduction.
