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Mechanical Cell Competition in Heterogeneous Epithelial Tissues.

Ryan J Murphy1, Pascal R Buenzli2, Ruth E Baker3

  • 1School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia. ryanjohn.murphy@hdr.qut.edu.au.

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|September 26, 2020
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Mechanical cell competition drives tissue development and aging. Our model shows mechanical differences, not just proliferation rates, can explain how cancer cells outcompete healthy cells in heterogeneous tissues.

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Area of Science:

  • * Biophysics
  • * Computational Biology
  • * Cancer Research

Background:

  • * Mechanical cell competition is crucial in tissue development, cancer, and aging.
  • * Cellular heterogeneity in stiffness and proliferation impacts tissue dynamics.
  • * Understanding these mechanical interactions is key for therapeutic strategies.

Purpose of the Study:

  • * To develop a 1D mechanical model for heterogeneous epithelial tissue dynamics.
  • * To investigate cell-length-dependent proliferation and death mechanisms.
  • * To explore how mechanical differences influence cancer cell competitiveness.

Main Methods:

  • * A discrete mechanical model incorporating stochastic proliferation and death.
  • * Derivation of a corresponding continuum model from the discrete model.
  • * Simulation of homogeneous tissue evolution and heterogeneous cancer-normal tissue competition.

Main Results:

  • * Demonstrated cancer cells can outcompete normal cells via mechanical advantages.
  • * Identified scenarios where mechanical factors are more critical than proliferative rates.
  • * Highlighted the importance of the discrete model for accurate continuum approximations.

Conclusions:

  • * Mechanical properties significantly influence cell competition in heterogeneous tissues.
  • * The developed model provides a framework to study cancer invasion mechanics.
  • * Caution is advised against oversimplified continuum models lacking discrete underpinnings.