Overriding native cell coordination enhances external programming of collective cell migration
| Autor: | Shim, Gawoon, Devenport, Danelle, Cohen, Daniel J. |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
coordinated motion Cell 02 engineering and technology electrotaxis Cell Line Collective migration Mice 03 medical and health sciences Cell Movement Cell Adhesion medicine Animals Humans Calcium chelators Skin 030304 developmental biology Wound Healing 0303 health sciences collective cell migration Multidisciplinary Chemistry Cadherin Collective cell migration E-cadherin Cell migration Adhesion Biological Sciences Cadherins 021001 nanoscience & nanotechnology Cell biology Intercellular Junctions medicine.anatomical_structure Mouse skin cell–cell adhesion Wounds and Injuries Calcium Applied Biological Sciences 0210 nano-technology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2101352118 |
| Popis: | Significance As collective cellular migration is critical for multicellular processes such as healing, approaches to reprogram it are of great interest. However, little is known about what happens when external “commands” clash with natural collective behaviors in a tissue. We investigate this question using a bioelectric stimulus—electrotaxis—to externally program cell migration in large, cultured layers of primary mouse skin monolayers, demonstrating how strong endogenous cell coordination competes with external migration commands, reducing tissue responsiveness to the commands and even causing significant cellular damage. However, we show that specifically weakening natural cell coordination by disrupting E-cadherin–mediated cell–cell adhesion improves our ability to control collective cell migration. These results offer a general approach to externally controlling highly coordinated tissues. 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. |
| Databáze: | OpenAIRE |
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