Differential Homeostasis of Sessile and Pendant Epithelium Reconstituted in a 3D-Printed “GeminiChip”

Pingqiang Cai, Zhuyun Li, Ela Sachyani Keneth, Luying Wang, Changjin Wan, Ying Jiang, Benhui Hu, Yun Long Wu, Shutao Wang, Chwee Teck Lim, Eugene V. Makeyev, Shlomo Magdassi*, Xiaodong Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
206 Downloads (Pure)

Abstract

Local mechanical cues can affect crucial fate decisions of living cells. Transepithelial stress has been discussed in the context of epithelial monolayers, but the lack of appropriate experimental systems leads current studies to approximate it simply as an in-plane stress. To evaluate possible contribution of force vectors acting in other directions, double epithelium in a 3D-printed “GeminiChip” containing a sessile and a pendant channel is reconstituted. Intriguingly, the sessile epithelia is prone to apoptotic cell extrusion upon crowding, whereas the pendant counterpart favors live cell delamination. Transcriptome analyses show upregulation of RhoA, BMP2, and hypoxia-signaling genes in the pendant epithelium, consistent with the onset of an epithelial–mesenchymal transition program. HepG2 microtumor spheroids also display differential spreading patterns in the sessile and pendant configuration. Using this multilayered GeminiChip, these results uncover a progressive yet critical role of perpendicular force vectors in collective cell behaviors and point at fundamental importance of these forces in the biology of cancer.

Original languageEnglish
Article number1900514
JournalADVANCED MATERIALS
Volume31
Issue number28
Early online date12 May 2019
DOIs
Publication statusPublished - 12 Jul 2019

Keywords

  • 3D printing
  • epithelial homeostasis
  • mechanobiology
  • organ-on-a-chip
  • tumor spheroids

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