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Related Experiment Video

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Study of Cell Migration in Microfabricated Channels
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High-Content Analysis of Cell Migration Dynamics within a Micropatterned Screening Platform.

Filipe V Almeida1, Luke Gammon1, Ana C Laly1

  • 1Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Advanced Biosystems
|July 11, 2020
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Summary

A new high-throughput assay precisely controls cell-matrix interactions to study cell migration. This method identified epigenetic inhibitors that enhance keratinocyte migration by remodeling the cytoskeleton.

Keywords:
EZH2animal replacementcell migrationepigeneticshigh-throughput

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biomaterials Science

Background:

  • Cell migration is crucial for development and wound repair, influenced by microenvironment and gene expression.
  • Understanding cell migration requires precise control over cell-matrix interactions and analysis of cytoskeletal dynamics.

Purpose of the Study:

  • To develop a high-throughput, quantitative assay for studying cell migration.
  • To identify novel therapeutic targets for enhancing wound repair by screening epigenetic inhibitors.

Main Methods:

  • Development of a high-throughput cell migration assay using micropatterned, dynamically adhesive polymer brush substrates in a 96-well format.
  • Automated imaging and quantitation of cell motility and F-actin cytoskeleton organization for high-content analysis.
  • Screening of 147 epigenetic inhibitors to identify compounds affecting cell migration.

Main Results:

  • The assay enabled precise control over cell-matrix interactions and high-content analysis of cell migration phenotypes.
  • Identification of EZH2-specific inhibitors that promote cytoskeletal remodeling and accelerate keratinocyte migration.
  • Demonstration that these inhibitors derepress an epithelial to mesenchymal transition-like gene expression program.

Conclusions:

  • The developed high-throughput micropatterned assay is a powerful tool for discovering therapeutic targets.
  • This platform facilitates dissection of complex gene-environment interactions relevant to wound repair and cell migration.