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Intercellular adhesion boots collective cell migration through elevated membrane tension.

Brent M Bijonowski1, Jongkwon Park1, Martin Bergert2

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Cell-cell adhesion alone can drive collective cell migration. This process involves increased membrane tension, activating phospholipase D2 and mammalian target of rapamycin signaling.

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Area of Science:

  • Cell Biology
  • Biophysics

Background:

  • Cell migration is crucial for multicellular processes like development and healing.
  • Cell-cell adhesions, often mediated by cadherins, link cytoskeletons and influence collective cell movement.
  • The role of plasma membrane signaling independent of cytoskeletal linkage in cell migration is not fully understood.

Purpose of the Study:

  • To investigate if intercellular binding alone, without direct cytoskeletal connection, can trigger collective cell migration.
  • To identify the signaling pathways involved in membrane-mediated collective cell dynamics.

Main Methods:

  • Utilized artificial photoswitchable cell-cell adhesions to connect adjacent plasma membranes.
  • Manipulated cell-cell adhesions without directly linking to cytoskeletal elements.
  • Measured membrane tension and downstream signaling molecules.

Main Results:

  • Artificial intercellular adhesions were sufficient to induce collective cell migration.
  • Increased membrane tension was observed upon cell linking.
  • Activation of phospholipase D2 and subsequent increase in phosphatidic acid were detected.
  • Mammalian target of rapamycin (mTOR) signaling was stimulated.

Conclusions:

  • Intercellular adhesions can initiate collective cell migration independently of cytoskeletal coupling.
  • A novel membrane-based signaling axis, involving membrane tension, phospholipase D2, phosphatidic acid, and mTOR, promotes collective cell dynamics.