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Cell-Substrate Interactions Feedback to Direct Cell Migration along or against Morphological Polarization
Girish Kumar1, Chia-Chi Ho1, Carlos C Co1
1Biomedical, Chemical, and Environmental Engineering, University of Cincinnati, Cincinnati, OH, 45221-0012, United States of America.
Cell polarization initially directs cell migration, but subsequent cellular responses can reverse this direction. RhoA promotes motility, while Cdc42 affects speed, not direction, on micropatterns.
Area of Science:
- Cell Biology
- Biophysics
- Mechanobiology
Background:
- Cells typically polarize and migrate towards their leading edge in response to stimuli.
- This process is thought to be initiated by initial cell polarization.
Purpose of the Study:
- To investigate the dynamic interplay between initial cell polarization and subsequent cell migration direction.
- To differentiate substrate-directed migration from gradient-induced chemotaxis.
Main Methods:
- Utilized microfabrication to precisely control cell morphology and migration paths.
- Employed constitutively active RhoA mutants and manipulated Cdc42 activity.
Main Results:
- Demonstrated that lamellipodia extension and attachment can override initial polarization, reversing migration direction.
- Observed faster migration along the initial polarization direction and slower migration against it.
- Found RhoA enhances motility regardless of migration direction, while Cdc42 impacts speed but not directionality on micropatterns.
Conclusions:
- Initial cell polarization does not solely determine migration direction; subsequent cellular dynamics can induce reversals.
- Substrate-directed cell migration exhibits distinct regulatory mechanisms compared to chemotaxis-driven migration.
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