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Cellular Environment and Phenotypic Heterogeneity: How Data-Driven Modeling Finds the Smoking Gun.

Marie Guilbert1, Emmanuel Courtade1, Quentin Thommen2

  • 1CNRS, UMR 8523-PhLAM-Physique des Lasers Atomes et Molécules, University of Lille, F-59000 Lille, France.

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Summary
This summary is machine-generated.

Collagen type I impacts cellular stress response heterogeneity by increasing a key protein's expression. This study quantifies this effect using single-cell monitoring and mathematical modeling for proteotoxic stress in HeLa cells.

Keywords:
cellular stress responseextracellular matrixheat stressmathematical modelingphenotypic heterogeneitysingle celltime lapse microscopy

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Area of Science:

  • Cell Biology
  • Biophysics
  • Systems Biology

Background:

  • Cellular phenotypes, particularly stress responses, exhibit significant heterogeneity due to regulatory network properties.
  • The extracellular matrix, including collagen type I, is a critical component of the cellular environment influencing cell behavior.

Purpose of the Study:

  • To quantify and interpret the influence of collagen type I on the phenotypic heterogeneity of cellular stress responses.
  • To elucidate the molecular mechanisms underlying collagen type I-mediated changes in cellular response heterogeneity.

Main Methods:

  • Single-cell monitoring techniques to track cellular responses.
  • Mathematical modeling of cellular regulatory networks.
  • Statistical analysis of phenotypic heterogeneity.
  • Biochemical measurements for model validation.

Main Results:

  • Detailed statistical characterization of phenotypic heterogeneity in cellular responses.
  • Mathematical model explaining heterogeneity through increased average expression of a central regulatory protein.
  • Model predictions were validated by biochemical measurements.

Conclusions:

  • Collagen type I significantly impacts cellular stress response heterogeneity.
  • An increase in the average expression of a central protein is a key mechanism driving these changes.
  • The presented framework offers a general methodology for studying phenotypic heterogeneity in cellular responses, exemplified by proteotoxic stress in HeLa cells.