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Successful development of tissue structures requires different collective cell migration patterns or phenotypes. Two examples of collective migration phenotypes in epithelial morphogenic processes, such as tubulogenesis, are rotational and invasive. Rotational collective migration phenotypes (RCM) typically lead to acinar structures, and invasive collective migration (ICM) phenotypes lead to duct-like structures. How cells adopt these different phenotypes is still largely unknown. Here, we investigate how cell–cell adhesion marker P-cadherin (CDH3) and mechanical cell–matrix interactions, including matrix deformations, protrusions, and focal adhesions, control rotational or invasive phenotypes during tubulogenesis. To accomplish our objective, we created a custom 3D microfluidic assay to perform live-cell imaging of epithelial clusters or cysts [wild-type (WT) and CDH3-depleted (CDH3-/-)] undergoing tubulogenesis, while simultaneously measuring matrix deformation rates. Our findings reveal WT epithelial cysts maintain rotational phenotypes, but transition to an invasive phenotype to undergo tubulogenesis. Furthermore, we demonstrate ICM phenotypes correlate with higher matrix deformation rates compared to rotational phenotypes. Our studies reveal CDH3 is required for epithelial cysts to transition from rotational to ICM phenotypes, associated with decreased matrix deformation rates. Without CDH3, epithelial cysts lose their ability to adopt ICM phenotypes, which can be rescued by RhoA activation. Finally, we demonstrate that the RhoA-rescued ICM phenotype is mediated, in part, by increased matrix deformation rates and vinculin recruitment to focal adhesion sites.
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This content will become publicly available on February 5, 2026
Mechanical feedback links cell division and dynamics in growing cell collectives
Local stresses in a tissue, a collective property, links cell division and dynamics.
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- Award ID(s):
- 2310639
- PAR ID:
- 10574642
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 21
- Issue:
- 6
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 1170 to 1179
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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