Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Biomedical Engineering
First Advisor
Christopher Lemmon
Abstract
Epithelial–mesenchymal transition (EMT) is a critical process underlying cancer progression, fibrosis, and tissue remodeling, characterized by coordinated changes in cell morphology, nuclear structure, and extracellular matrix (ECM) organization. Transforming growth factor beta 1 (TGF-β1) is a primary inducer of EMT; however, the extent to which integrin-mediated signaling and ECM remodeling regulate these structural changes remains incompletely understood. In this study, we quantitatively investigated EMT-associated remodeling in A549 lung carcinoma cells and MCF10A epithelial cells following TGF-β1 stimulation. Cells were cultured on ECM-coated substrates and treated with TGF-β1 in the presence or absence of integrin-targeting inhibitors (ATN-161, 28-G11, and STX-100). Im munofluorescence imaging was combined with a custom computational image analysis pipeline to extract multi-scale features, including cell morphology, nuclear morphol viii ogy, and fibronectin fibril organization. TGF-β1 treatment induced significant increases in cell area, nuclear size, and nuclear eccentricity, consistent with EMT-associated structural remodeling. Inte grin inhibition revealed distinct functional differences between pathways. ATN-161 partially attenuated TGF-β1-induced increases in cell spreading and nuclear enlarge ment, indicating a role for integrin-mediated signaling in regulating EMT-associated morphology. In contrast, 28-G11 and STX-100 exhibited minimal inhibitory effects, suggesting that not all integrin pathways contribute equally to TGF-β1-driven re modeling. These trends were consistent across both epithelial and cancer cell models, highlighting cell-type-dependent but conserved responses. Overall, this work demonstrates that EMT-associated structural changes can be quantitatively characterized across multiple biological scales and reveals differential roles of integrin-mediated pathways in regulating TGF-β1-induced remodeling. These f indings provide insight into the mechanobiological regulation of EMT and establish a quantitative framework for evaluating ECM and integrin contributions to cellular phenotype
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-7-2026