High-Content Analysis of Cell Migration Dynamics within a Micropatterned Screening Platform.

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.