Biomechanics Approach and Mechanical Biomarkers for Cancer Detection: A Case Study of Triple-Negative Breast Cancer

Abstract

This thesis explores the cytoskeletal structures and the statistical variations in the cell-protein fluorescence intensities/volume densities, creep characteristics, and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at different stages of metastases. Most of the cytoskeletal proteins, such as actin contents of the cell cytoskeletal structures are shown to decrease significantly with cell progression from non-tumorigenic to more metastatic states. The corresponding creep and viscoelastic properties of the nuclei and the cytoplasm (Young’s moduli, viscosities, and relaxation times) of the cells are also measured using Digital Image Correlation (DIC) and shear assay techniques. The study reveals significant differences between the creep and viscoelastic properties of non-tumorigenic breast cells versus tumorigenic cells. These are shown to exhibit statistical variations that are well characterized by normal distributions. The changes in the mean properties of individual cancer cells are tested using Fisher pairwise comparisons and the analysis of variance (ANOVA). The probabilistic implications of the results are then discussed for the development of shear assay techniques and mechanical biomarkers for the detection of triple-negative breast cancer at different stages of progression.