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Access Type
WSU Access
Date of Award
January 2024
Degree Type
Thesis
Degree Name
M.S.
Department
Biomedical Engineering
First Advisor
Jitao Zhang
Abstract
According to the World Health Organization, breast cancer is the most prevalent cancer worldwide as of 2023. It has been evidenced that breast cancer progression is regulated by multiple factors. Among them, biomechanics plays an important role through the mechanism of mechanotransduction. In comparison to healthy cells, tumor cells are softer and more flexible to adjust their stiffness in response to mechanical cues from their microenvironment. While the biomechanics of tumor cells has been extensively studied in vitro, most of the mechanical measurements are conducted in 2D culturing conditions, which cannot recapitulate the important features of 3D physiological tissue. Tumor spheroids cultured in 3D microenvironments is evidenced to be more physiologically relevant than 2D cultures. However, existing techniques for measuring mechanical properties cannot probe 3D biomechanics because they are generally contact-based and invasive. The purpose of this study was to reveal the mechanical evolution of cancer cells within multicellular spheroids by using an innovative all-optical technique, Brillouin microscopy. First, this work has validated the measured Brillouin modulus via comparison with an existing contact-based technique, namely atomic force microscopy, with single cells. Next, the mechanical properties of the spheroids were monitored by Brillouin microscopy as they grow, allowing quantification of the different mechanical behaviors observed in healthy and tumor spheroids. This research provides direct evidence regarding the biomechanics of cancer cells during tumor growth in 3D, which is an important complement to the existing knowledge based on 2D cell cultures. Our findings demonstrate significant differences in the Brillouin shift between MCF10A and MCF10CA1h when cultured in 3D matrices. This suggests that the mechanical properties measured via Brillouin microscopy could serve as a promising biomarker for assessing the relative metastatic potential of both non-tumorigenic and malignant mammary epithelial spheroids, and potentially across various cancer cell lines. The outcome of this work can potentially serve as a new method to evaluate the performance of cancer therapies and drug screening in both preclinical and clinical studies for cancer prevention.
Recommended Citation
Hilai, Karlin Wisam, "Biomechanical Properties Of Breast Tumor Spheroids Measured By Brillouin Microscopy" (2024). Wayne State University Theses. 945.
https://digitalcommons.wayne.edu/oa_theses/945