Mechanobiological Effects of Residual Stress on Epithelial Cell MorphologydissertationsYang, DingyicreatorGray, MarissaReaderBeveridge, JilianReaderSrivastava, VikasAdvisorBrown University. Biology and Medicine: Biomedical Engineeringsponsor2025, None p.born digitalThesis (Sc. M.)--Brown University, 2025thesesCell adhesion and spreading are critical processes in mechanobiology, influenced by extracellular matrix mechanics and substrate properties. While substrate stiffness has been extensively studied, the effects of residual stress on cellular behavior remain largely unexplored. This study examines the impact of residual stress on MCF-10A epithelial cells seeded on prestretched polydimethylsiloxane (PDMS) substrates with stiffness values of 1000 kPa, 100 kPa, and 50 kPa. Cell attachment, spreading, and morphological changes were assessed through fluorescence imaging, image analysis, and statistical evaluation. The findings reveal that stress significantly reduces cell spreading across all stiffness conditions, as evidenced by decreased cell areas on stretched substrates compared to controls. Cells tend to avoid regions of higher residual stress, as cell attachment was markedly lower on stretched substrates. Despite statistical differences in cell aspect ratio, these variations were minor and did not indicate a biologically significant effect of residual stress on cell elongation. These results suggest that residual stress acts as a mechanical regulator of cell adhesion and spreading, which impose constraints on cellular expansion. The study brings a very new insight that needs to be mechanistically understood and incorporated into existing mechanotransduction models that primarily focus on stiffness as the dominant cue. The findings of this work highlight the necessity of incorporating residual stress into experimental and modeling frameworks.Cells--Mechanical propertiesmechanobiologyEnglishRPB20250707