Collective cell migration has distinct directionality and speed dynamics
- 967 Downloads
When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique—Particle Image Velocimetry (PIV)—we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell–cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.
KeywordsWound healing Cell contractility PDMS Corneal epithelial cell Cell communication Blebbistatin
Particle image velocimetry
This work was supported by NIH EY019101(to. M.Z.) and AFOSR FA9550-16-1-0052 (to M.Z.). This study was supported in part by the Major Program Grant of Zhejiang Provincial Science and Technology (No. 2012C03007-6) (to Z.X.), NIH GM 68952 (to A.M.), an Unrestricted Grant from Research to Prevent Blindness, Inc. (to M.Z.), and an NEI core grant (to M.Z.). We thank Dr. James Jester (UC Irvine), Dr. Vijay Krishna Raghunathan and Dr. Christopher J. Murphy (UC Davis) for the generous gift of the hTCEpi cell, Brian Reid (UC Davis) for English editing and proofreading. Y.Z. is supported by a fellowship from the China Scholarship Council. F. Lin thanks the support from a Collaborative Research Travel Grant provided by the Burroughs Wellcome Fund.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 6.Gruler H, Franke K (1990) Automatic control and directed cell movement. Novel approach for understanding chemotaxis, galvanotaxis, galvanotropism. J Biosci 45(11–12):1241–1249Google Scholar
- 9.Li L, Hartley R, Reiss B, Sun Y, Pu J, Wu D, Lin F, Hoang T, Yamada S, Jiang J, Zhao M (2012) E-cadherin plays an essential role in collective directional migration of large epithelial sheets. Cell Mol Life Sci 69(16):2779–2789. doi: 10.1007/s00018-012-0951-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Chepizhko O, Giampietro C, Mastrapasqua E, Nourazar M, Ascagni M, Sugni M, Fascio U, Leggio L, Malinverno C, Scita G, Santucci S, Alava MJ, Zapperi S, La Porta CA (2016) Bursts of activity in collective cell migration. Proc Natl Acad Sci USA 113(41):11408–11413. doi: 10.1073/pnas.1600503113 CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Raffel M, Willert CE, Kompenhans J (2013) Particle image velocimetry: a practical guide. Springer, New YorkGoogle Scholar