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                      TRENDING OPEN SCIENCE
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Cellular crowd control: overriding endogenous cell coordination makes
cell migration more susceptible to external programming
--------
By
  Gawoon Shim
  Danelle Devenport
  Daniel J. Cohen

DOI: 10.1101/2021.01.23.427700

On bioRxiv: https://biorxiv.org/content/10.1101/2021.01.23.427700v1

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, pre-
existing 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 pre-existing 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 to demonstrate accelerated wound closure in vitro. These
results are in keeping with those from diverse, non-cellular 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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