Measuring mechanical heterogeneities in live epithelia

The mechanical heterogeneity of biological tissues not only influences the tissue rigidity and cell migration, but also closely regulates essential biological processes such as organogenesis, homeostasis, and cancer invasion. However, experimentally measuring the modulus field in live epithelia has been challenging, as conventional tools (e.g., atomic force microscopy and rheometry) can be invasive, time-consuming, or lack cell-level resolution. In this work, we develop a method to visualize the heterogenous modulus distribution in live epithelial monolayers by integrating a cell stretcher, light microscopy, and artificial intelligence (AI)-based inference. Specifically, we capture the non-affine displacement of cells during extension and utilize AI models to translate such measurements into the modulus field. This experimental platform allows for a method to determine the correlation between cell modulus and morphological features including area and aspect ratio. Contrary to previous numerical studies, in which epithelial packing was suggested to be predominantly governed by geometric constraint, our results show that cell modulus variation plays an equally important role.