Mechanobiology of Breast Cancer

Abstract

Cancer progression is driven by complex interactions between tumor cells and their surrounding microenvironment, which together undergo profound physical and biological changes. A key aspect of this crosstalk is the alteration of biophysical properties in both cells and the extracellular matrix (ECM), influencing processes such as invasion and metastasis. This dissertation investigates these biophysical changes with a focus on rheology, which describes how materials deform and flow under stress.

We developed a microfluidic platform to dynamically compress breast cancer spheroids of varying malignancy, extracting their viscoelastic properties and linking them to cytoskeletal organization and cell–cell adhesion. The results show that malignant spheroids are softer, more deformable, and prone to fragmentation compared to benign ones, facilitating invasion under physical stress. Expanding the scope to the ECM, we studied collagen I matrices embedded with invasive breast cancer cells. Bulk rheology and rheoconfocal microscopy revealed that cancer cells actively remodel collagen networks, suppressing the typical stress-stiffening response and inducing time-dependent softening, in contrast to fibroblasts or passive inclusions.

Together, these findings provide new insights into how cancer cells and the ECM dynamically influence each other’s rheological properties. This dissertation highlights the importance of viscoelasticity in tumor progression and suggests future opportunities for translating such biophysical insights into diagnostic or therapeutic approaches.