Semester of Graduation

Spring 2024

Degree

Master of Science in Biological and Agricultural Engineering (MSBAE)

Department

Department of Biological and Agricultural Engineering

Document Type

Thesis

Abstract

In 2022, ~288,000 American women were diagnosed with metastatic breast cancer which was the leading cause of patient mortality with ~43,000 American women succumbing to the disease. Women can be diagnosed with four different molecular subtypes of breast cancer: luminal A, luminal B, human epithelial growth receptor type 2 enriched (HER2+), and triple-negative breast cancer (TNBC). TNBC accounts for ~12% of all breast cancers, yet it has the worst outcomes. TNBC is highly invasive, with ~46% of TNBC patients developing metastatic disease. A further understanding of metastatic TNBC is needed to provide a greater understanding of how to treat this cancer. During metastatic spread through the vasculature, cancer cells are exposed to fluid shear stress (FSS). The focus of this study is to investigate the role of FSS on the one-dimensional (1D) migration of TNBC. This is accomplished using a modular microfluidic approach consisting of two devices: one that first exposes cells to FSS and a second device that allows for 1D migration. The TNBC cell line, MDA-MB-231, were exposed to FSS using a serpentine microfluidic device at a physiologically relevant magnitude of (10 dyn/cm2) and then injected into a second device that consisted of an array of 200 µm long and 5 µm wide channels to recapitulate 1D migration during extravasation. The operating principles of the device were first optimized to ensure adequate cell seeding and the prevention of bubble nucleation during the 12 h migration experiment. The migratory potential of sheared cells was compared to a non-sheared control cohort to determine if exposure to FSS enhanced random migration. Migratory features that were evaluated were migration speed, distance, and displacement. Results across the entire population of cells demonstrate that there was no significant difference between any of the parameters (average speed and distance, total distance, and total displacement) of the sheared and non-sheared cells. Interestingly, single cell tracking analysis demonstrated that the migratory behavior between sheared cells and non-sheared cells appeared to differ in how the cells moved through the device. Sheared cells appeared to persistently traverse through the microchannels whereas non-sheared cells moved randomly within the migration device. These findings offer promising new insight into how exposure to FSS alters the metastatic potential of TNBC.

Date

4-5-2024

Committee Chair

Monroe, W. Todd

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Available for download on Saturday, April 05, 2025

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