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Abstract This perspective derives from the presentations and discussions on mechanobiology at the 2025 Cellular and Molecular Bioengineering Conference in San Diego. Mechanobiological processes play critical roles in tissue development, regeneration, and disease progression. Recent advances in engineering, biology, and medicine have enabled the translation of mechanobiology discoveries into clinical practice, giving rise to the emerging field of mechanomedicine. The development and application of engineering technology and tools have provided new insights into how mechanical cues regulate immune cell response, stem cell differentiation, cell migration, and cell metabolism. In this perspective, we highlight exciting discoveries and innovative tools in mechanobiology research, and discuss challenges that must be overcome to truly bridge the gap between mechanobiology and mechanomedicine. Graphical Abstract 

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.