Journal
ADVANCED MATERIALS
Volume 31, Issue 28, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201900514
Keywords
3D printing; epithelial homeostasis; mechanobiology; organ-on-a-chip; tumor spheroids
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Funding
- National Research Foundation, Prime Minister's Office, Singapore, under NRF Investigatorship [NRF2016NRF-NRFI001-21]
- Campus for Research Excellence and Technological Enterprise (CREATE) Programme of Nanomaterials for Energy and Water Management
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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.
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