Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability

Lucas Henrion, Juan Andres Martinez, Vincent Vandenbroucke, Mathéo Delvenne, Samuel Telek, Andrew Zicler, Alexander Grünberger and Frank Delvigne ()
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Lucas Henrion: University of Liège
Juan Andres Martinez: University of Liège
Vincent Vandenbroucke: University of Liège
Mathéo Delvenne: University of Liège
Samuel Telek: University of Liège
Andrew Zicler: University of Liège
Alexander Grünberger: Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology
Frank Delvigne: University of Liège

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Isogenic cell populations can cope with stress conditions by switching to alternative phenotypes. Even if it can lead to increased fitness in a natural context, this feature is typically unwanted for a range of applications (e.g., bioproduction, synthetic biology, and biomedicine) where it tends to make cellular response unpredictable. However, little is known about the diversification profiles that can be adopted by a cell population. Here, we characterize the diversification dynamics for various systems (bacteria and yeast) and for different phenotypes (utilization of alternative carbon sources, general stress response and more complex development patterns). Our results suggest that the diversification dynamics and the fitness cost associated with cell switching are coupled. To quantify the contribution of the switching cost on population dynamics, we design a stochastic model that let us reproduce the dynamics observed experimentally and identify three diversification regimes, i.e., constrained (at low switching cost), dispersed (at medium and high switching cost), and bursty (for very high switching cost). Furthermore, we use a cell-machine interface called Segregostat to demonstrate that different levels of control can be applied to these diversification regimes, enabling applications involving more precise cellular responses.

Date: 2023
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DOI: 10.1038/s41467-023-41917-z

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