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

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...

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Main Authors: Lucas Henrion, Juan Andres Martinez, Vincent Vandenbroucke, Mathéo Delvenne, Samuel Telek, Andrew Zicler, Alexander Grünberger, Frank Delvigne
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41917-z
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author Lucas Henrion
Juan Andres Martinez
Vincent Vandenbroucke
Mathéo Delvenne
Samuel Telek
Andrew Zicler
Alexander Grünberger
Frank Delvigne
author_facet Lucas Henrion
Juan Andres Martinez
Vincent Vandenbroucke
Mathéo Delvenne
Samuel Telek
Andrew Zicler
Alexander Grünberger
Frank Delvigne
author_sort Lucas Henrion
collection DOAJ
description 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.
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spelling doaj.art-bc5bf61e3a50412fa527608f1a0d36522023-11-20T10:10:25ZengNature PortfolioNature Communications2041-17232023-10-0114111310.1038/s41467-023-41917-zFitness cost associated with cell phenotypic switching drives population diversification dynamics and controllabilityLucas Henrion0Juan Andres Martinez1Vincent Vandenbroucke2Mathéo Delvenne3Samuel Telek4Andrew Zicler5Alexander Grünberger6Frank Delvigne7Terra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeMicrosystems in Bioprocess Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of TechnologyTerra Research and Teaching Centre, Microbial Processes and Interactions (MiPI), Gembloux Agro-Bio Tech, University of LiègeAbstract 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.https://doi.org/10.1038/s41467-023-41917-z
spellingShingle Lucas Henrion
Juan Andres Martinez
Vincent Vandenbroucke
Mathéo Delvenne
Samuel Telek
Andrew Zicler
Alexander Grünberger
Frank Delvigne
Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Nature Communications
title Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
title_full Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
title_fullStr Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
title_full_unstemmed Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
title_short Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
title_sort fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
url https://doi.org/10.1038/s41467-023-41917-z
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