Cellular and Molecular Life Sciences

, Volume 69, Issue 16, pp 2779–2789 | Cite as

E-cadherin plays an essential role in collective directional migration of large epithelial sheets

  • Li Li
  • Robert Hartley
  • Bjoern Reiss
  • Yaohui Sun
  • Jin Pu
  • Dan Wu
  • Francis Lin
  • Trung Hoang
  • Soichiro Yamada
  • Jianxin Jiang
  • Min Zhao
Research Article

Abstract

In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell–cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell–cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell–cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism—E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets.

Keywords

Collective cell migration Electric fields Galvanotaxis/electrotaxis E-cadherin Cell–cell adhesion Traction force 

Supplementary material

18_2012_951_MOESM1_ESM.ppt (4.1 mb)
Supplementary material 1 (PPT 4315 kb)

Video S1 Collective electrotaxis of MDCK II cells in monolayer, but not in isolation. Time is in hh:mm style. (MPG 1484 kb)

Video S2 MDCK II cell sheets respond to EFs in a size-dependent manner. Time is in hh:mm style. (MPG 1484 kb)

Video S3 Better collective electrotaxis in monolayer than in isolation in various types of cells. Time is in hh:mm style. (MPG 585 kb)

18_2012_951_MOESM5_ESM.mpg (1.4 mb)
Video S4 E-cadherin mediated cell-cell adhesion is required for EF-guiding migration of MDCK I cells in a monolayer. Time is in hh:mm style. (MPG 1484 kb)
18_2012_951_MOESM6_ESM.mpg (2.3 mb)
Video S5 Traction force re-orientation at the leading edges of cell groups in an EF. Time is in hh:mm style. (MPG 2312 kb)

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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Li Li
    • 1
    • 2
  • Robert Hartley
    • 3
  • Bjoern Reiss
    • 3
  • Yaohui Sun
    • 1
  • Jin Pu
    • 3
  • Dan Wu
    • 4
  • Francis Lin
    • 4
  • Trung Hoang
    • 5
  • Soichiro Yamada
    • 5
  • Jianxin Jiang
    • 2
  • Min Zhao
    • 1
  1. 1.Department of Dermatology, School of Medicine, Institute for Regenerative CuresUniversity of California at DavisSacramentoUSA
  2. 2.State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping HospitalThird Military Medical UniversityChongqingChina
  3. 3.School of Medical Sciences, Institute of Medical SciencesUniversity of AberdeenAberdeenUK
  4. 4.Department of Physics and AstronomyUniversity of ManitobaWinnipegCanada
  5. 5.Department of Biomedical EngineeringUniversity of California at DavisDavisUSA

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