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Updated: Jun 7, 2025
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Src kinase slows collective rotation of confined epithelial cell monolayers
Nastassia Pricoupenko1, Flavia Marsigliesi1, Philippe Marcq2
1Physics of Cells and Cancer, Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, 75005 Paris, France. isabelle.bonnet@sorbonne-universite.fr.
Abstract:
Collective cell migration is key during development, wound healing, and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a key signalling protein for the physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its overactivation is associated with cancer aggressiveness. Here, we take advantage of optogenetics to precisely control Src activation in time and show that its pathological-like activation slows the collective rotation of epithelial cells confined into circular adhesive patches. We interpret velocity, force, and stress data during period of non-activation and period of activation of Src thanks to a hydrodynamic description of the cell assembly as a polar active fluid. Src activation leads to a 2-fold decrease in the ratio of polar angle to friction, which could result from increased adhesiveness at the cell-substrate interface. Measuring internal stress allows us to show that active stresses are subdominant compared to traction forces. Our work reveals the importance of fine-tuning the level of Src activity for coordinated collective behaviors.
Insights
Pathological Src kinase activation slows collective epithelial cell rotation. Fine-tuning Src activity is crucial for coordinated cell behaviors in development and disease.
Area of Science:
- Cell biology
- Biophysics
- Cancer research
Background:
- Collective cell migration is vital for development, wound healing, and metastasis.
- Src kinase regulates epithelial cell functions like adhesion, motility, and mechanotransduction.
- Overactivated Src kinase is linked to increased cancer aggressiveness.
Purpose of the Study:
- To investigate the impact of precisely controlled Src kinase activation on collective cell migration.
- To understand the biophysical mechanisms underlying Src-mediated regulation of cell behavior.
Main Methods:
- Utilized optogenetics to control Src kinase activation in time.
- Employed a hydrodynamic description of cells as a polar active fluid.
- Analyzed velocity, force, and stress data during Src activation and non-activation periods.
Main Results:
- Pathological-like Src activation significantly slowed the collective rotation of epithelial cells in circular patches.
- Src activation decreased the ratio of polar angle to friction by twofold, suggesting increased cell-substrate adhesion.
- Active stresses were found to be subdominant compared to traction forces.
Conclusions:
- Src kinase activity level critically influences coordinated collective cell behaviors.
- Modulating Src activity is important for understanding and potentially treating conditions involving collective cell migration, such as cancer metastasis.
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