Collective cell guidance by cooperative intercellular forces.

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cellular migration is fundamental to tissue development and repair.
• Understanding the coordination of collective cell migration in multicellular assemblies has been limited by the inability to experimentally measure mechanical stresses at cell-cell junctions.

Purpose of the Study:

• To map mechanical stresses within and between cells in a monolayer.
• To investigate how these stresses influence collective cell migration.
• To identify unifying principles governing collective cell migration across different cell types.

Main Methods:

• Developed novel experimental techniques to map mechanical stresses within and between cells in a monolayer.
• Analyzed stress fluctuations and their correlation with cellular migration patterns.
• Examined endothelial, epithelial, and breast cancer cell lines.

Main Results:

• Observed spontaneous, severe fluctuations of mechanical stress within cell monolayers.
• Demonstrated that local cellular migrations align with local orientations of maximal principal stress.
• Found that this behavior is consistent in endothelial and epithelial monolayers, and in breast cancer cells before the epithelial-mesenchymal transition.

Conclusions:

• Collective cell migration is governed by mechanical stress landscapes.
• A unifying principle involves cells transmitting normal stress across junctions and migrating along minimal shear stress orientations.
• This principle applies to diverse cell types and may be altered during disease progression, such as cancer metastasis.