Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 29, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2101352118
Keywords
collective cell migration; electrotaxis; coordinated motion; E-cadherin; cell-cell adhesion
Categories
Funding
- Princeton Catalysis Initiative
- NIH [R35 GM13357403]
- National Science Foundation CAREER Award [2046977]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [2046977] Funding Source: National Science Foundation
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Collective cell migration is crucial in various biological processes, and external programming of cell migration can be valuable. However, challenges may arise when external commands interfere with preexisting collective behaviors in tissues or systems. By reducing preexisting coordination through weakening cell-cell adhesion, control of collective migration can be improved, leading to accelerated wound closure.
As collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, preexisting collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue-electrical stimulation and electrotaxis-to primary mouse skin monolayers where we can tune cell-cell adhesion strength to modulate endogenous collectivity. Monolayers with high cell-cell adhesion showed strong natural coordination and resisted electrotactic control, with this conflict actively damaging the leading edge of the tissue. However, reducing preexisting coordination in the tissue by specifically inhibiting E-cadherin-dependent cell- cell adhesion, either by disrupting the formation of cell-cell junctions with E-cadherin-specific antibodies or rapidly dismantling E-cadherin junctions with calcium chelators, significantly improved controllability. Finally, we applied this paradigm of weakening existing coordination to improve control and demonstrate accelerated wound closure in vitro. These results are in keeping with those from diverse, noncellular systems and confirm that endogenous collectivity should be considered as a key quantitative design variable when optimizing external control of collective migration.
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