Cell crawling mediates collective cell migration to close undamaged epithelial gaps.
Fundamental biological processes such as morphogenesis and wound healing involve the closure of epithelial gaps. Epithelial gap closure is commonly attributed either to the purse-string contraction of an intercellular actomyosin cable or to active cell migration, but the relative contribution of these two mechanisms remains unknown. Here we present a model experiment to systematically study epithelial closure in the absence of cell injury. We developed a pillar stencil approach to create well-defined gaps in terms of size and shape within an epithelial cell monolayer. Upon pillar removal, cells actively respond to the newly accessible free space by extending lamellipodia and migrating into the gap. The decrease of gap area over time is strikingly linear and shows two different regimes depending on the size of the gap. In large gaps, closure is dominated by lamellipodium-mediated cell migration. By contrast, closure of gaps smaller than 20 μm was affected by cell density and progressed independently of Rac, myosin light chain kinase, and Rho kinase, suggesting a passive physical mechanism. By changing the shape of the gap, we observed that low-curvature areas favored the appearance of lamellipodia, promoting faster closure. Altogether, our results reveal that the closure of epithelial gaps in the absence of cell injury is governed by the collective migration of cells through the activation of lamellipodium protrusion.
Laboratoire Matière et Systèmes Complexes,  Université Paris Diderot and Unité Mixte de Recherche 7057 Centre National de la Recherche Scientifique, F-75205 Paris Cedex 13,  France.
Ester
E
Anon
Xavier
X
Serra-Picamal
Pascal
P
Hersen
Nils C
NC
Gauthier
Michael P
MP
Sheetz
Xavier
X
Trepat
Benoît
B
Ladoux
D000205:Actomyosin / Q000502:physiology; D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D007365:Intercellular Junctions / Q000502:physiology; D007668:Kidney / Q000166:cytology; D009219:Myosin-Light-Chain Kinase / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology*; D013314:Stress, Mechanical; D014945:Wound Healing / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology
D000205:Actomyosin; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase