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Predicting Collective Migration of Cell Populations Defined by Varying Repolarization Dynamics
Jairaj Mathur1, Bapi Sarker1, Amit Pathak1
1Department of Mechanical Engineering & Materials Science, Washington University, St. Louis, Missouri.
Biophysical Journal
|December 12, 2018
Summary
Cell repolarization dynamics influence collective migration. Cells repolarizing slower become elongated and lead migration, impacting tissue development and disease progression.
Area of Science:
- Cell biology
- Biophysics
- Computational biology
Background:
- Collective cell migration is crucial for development and disease.
- Cell polarity, force generation, and adhesion drive migration.
- The role of dynamic cell repolarization in collective migration remains unclear.
Purpose of the Study:
- To investigate how individual cell repolarization dynamics regulate collective cell migration.
- To model the impact of varying repolarization intervals on cell shape and migration speed.
- To identify and characterize 'leader' cells based on repolarization behavior.
Main Methods:
- Developed a vertex-based computational model of deformable cells.
- Simulated cell migration with random repolarization at defined intervals.
- Experimentally imaged high-resolution epithelial cell monolayers during collective migration.
- Defined 'leader' cells by long repolarization intervals and minimal contact.
Main Results:
- Simulations showed longer repolarization intervals lead to cell elongation, faster migration, and increased cell sheet deformation.
- Experimental data confirmed leading edge cells had longer repolarization intervals and more elongated shapes.
- Placing 'mutant leader' cells (long repolarization interval) at the leading edge significantly increased collective migration speed.
Conclusions:
- Cell repolarization dynamics are a key determinant of collective migration modes.
- A minority of cells with specific repolarization behaviors can profoundly influence population-level migration.
- This model provides insights into collective cell migration in development and diseases like cancer.
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