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Understanding the Biophysical and Metabolic Regulations of the Epithelial Jamming Transition
- Bermudez, Alexandra Gabrielle
- Advisor(s): Lin, Neil Y.C.
Abstract
Epithelial cells play a crucial role as they line every organ in our bodies and perform essential physiological functions. During the development of epithelial tissue, injury repair, or wound healing, these cells undergo cell crowding – a canonical tissue process where the cells continuously migrate and proliferate until they form a tightly packed, quiescent layer. To understand the underlying mechanism of such a “fluid-to-solid” transition in epithelia, researchers have successfully utilized the jamming transition framework to describe its physical control parameters including cell density, morphology, and motility. However, the molecular events governing these control parameters, as well as their downstream biological impacts, remain relatively underexplored. In my thesis, I developed a platform for investigating the modulus heterogeneity in a live monolayer to identify a correlation between cell size and stiffness, facilitating a deeper understanding of how cell mechanical properties influence morphological phenotype. I then combined transcriptomics and metabolomics to characterize cell behavior during crowding and identified the functional role of cell metabolism in regulating cell motility. I then described the origin of morphological heterogeneity in epithelial monolayers and how such heterogeneity can promote variations in gene expression.
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