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Collective 3D Migration of Embryonic Epithelial Mesenchymal Composite Tissues are Regulated by Surface Topology

2015

Article

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Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topology. Most studies on surface topology and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multicellular tissues to topological cues. Here, we examine the behaviors of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis to complex topological cues. We control topology using fabricated micropost arrays (MPAs) with different diameters (e.g., different spacing gaps) and investigate the collective 3D migration of these multicellular systems in these MPAs. Our topographical controlled approach for cellular application enables us to achieve a high degree of control over micropost positioning and geometry via simple, accurate, and repeatable microfabrication processes. We find that the topology regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing within MPAs we discover a role for topology in disrupting collective enhancement of cell migration. We find 3D topological cues can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement.

Author(s): Song, Jiho and Shawky, Joe and Kim, Yong Tae and Hazar, Melis and Sitti, Metin and LeDuc, Philip R and Davidson, Lance A
Journal: Biophysical Journal
Volume: 108
Number (issue): 2
Pages: 455a
Year: 2015
Month: January
Day: 27
Publisher: Elsevier

Department(s): Physical Intelligence
Bibtex Type: Article (article)

DOI: 10.1016/j.bpj.2014.11.2484

BibTex

@article{song2015collective,
  title = {Collective 3D Migration of Embryonic Epithelial Mesenchymal Composite Tissues are Regulated by Surface Topology},
  author = {Song, Jiho and Shawky, Joe and Kim, Yong Tae and Hazar, Melis and Sitti, Metin and LeDuc, Philip R and Davidson, Lance A},
  journal = {Biophysical Journal},
  volume = {108},
  number = {2},
  pages = {455a},
  publisher = {Elsevier},
  month = jan,
  year = {2015},
  month_numeric = {1}
}