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Leader-cell-driven epithelial sheet fingering.

Yanjun Yang1, Herbert Levine2,3

  • 1Department of Applied Physics and Center for Theoretical Biological Physics, Rice University, Houston, TX 77251-1892, United States of America.

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|May 6, 2020
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Summary
This summary is machine-generated.

Leader cells are essential for collective cell migration and the formation of finger-like protrusions in epithelial cell layers. While supracellular actin cables aid finger shape, they are not required for initial finger formation.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Computational Biology

Background:

  • Collective cell migration is vital for tissue development and disease progression.
  • Epithelial cell layers migrating collectively often form finger-like protrusions at their leading edge.
  • These protrusions are typically guided by specialized leader cells.

Purpose of the Study:

  • To develop and validate a computational model for collective cell migration and fingering instability.
  • To investigate the roles of leader cells and supracellular actin cables in this process.
  • To understand the underlying mechanisms driving finger formation in epithelial monolayers.

Main Methods:

  • Developed a subcellular-element-based computational model for epithelial cell monolayers.
  • Incorporated leader cell behavior and supracellular actin cable dynamics.
  • Compared model predictions with experimental data on Madin-Darby canine kidney cells.
  • Analyzed the system using a continuum active fluid model.

Main Results:

  • The model accurately reproduced experimental traction force patterns and velocity fields.
  • Leader cells were predicted as necessary for stable finger pattern formation and maintenance.
  • Supracellular actin cables were found to maintain finger shape but not initiate finger formation.
  • Homogeneous active fluid models without leader cells failed to produce finger protrusions.

Conclusions:

  • Leader cells play a critical, indispensable role in initiating and sustaining collective cell migration fingering instability.
  • Supracellular actin cables are important for stabilizing finger morphology but not for their emergence.
  • The computational model provides a valuable tool for studying cell migration dynamics and guiding future experiments.