WITH NATHAN THOMAS, BRAULIO ORTEGA QUESADA, AND DR. ADAM MELVIN, DEPARTMENT OF CHEMICAL AND BIOMOLECULAR ENGINEERING
Human cells experience a variety of biophysical forces in vivo that significantly alter biological processes and cellular phenotype. One such force is cellular deformation, which can occur during transendothelial migration or transit through narrow capillaries. While the biophysical changes in cells due to deformation have been well studied, the phenotypic changes induced by deformation driving pro-survival behavior have been understudied. This work aimed to provide new insight into biochemical changes, such as altered proliferation or protein phosphorylation, during biophysical interrogation in single breast cancer cells. This was accomplished by developing a modular microfluidic device with the capability to mimic the biophysical forces endured during metastasis. Cells were deformed through a constriction channel and collected in a microwell array for single-cell immunostaining utilizing fluorescence microscopy. The estrogen receptor-positive (ER+) and triple-negative breast cancer (TNBC) subtypes were studied due to prior work suggesting cell subtype impact on biochemical pathways. Single MCF-7 (ER+ cell line) deformed cells exhibited decreased levels of the proliferative marker Ki67 compared to non-deformed control cells. Single non-deformed MDA-MB-231 cells (TNBC cell line) exhibited increased levels of p-AKT. These initial findings support that the biochemical changes under deformation appear subtype-specific and result in different protein phosphorylation and proliferation levels. Development and Optimization of a Modular Microfluidic Device to Study the Effects of Deformation on Metastatic Breast Cancer
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