Adherence Rates, Morphology and Force Depend on Microenvironment Stiffness and Metastatic Potential in Breast Cancer Cells

Cell adhesion plays an important role in the normal functions of cells, including contraction, spreading, crawling, and invasion. In cancer cells, adhesion regulates migration and invasiveness, and following biochemical attachment, depends mainly on the stiffness of the matrix surrounding a tumor. In the current work we show that the rate of adhesion, dynamic cell morphology and forces applied during adhesion vary between benign and cancer cells. Thus, through measurements of those differences and while varying substrate-stiffness we can determine malignancy and metastatic potential (MP) of cancer cells. We evaluate the rate of attachment from suspension on a 2D collagen-coated polyacrylamide gel, concurrently with changes in cell morphology and the strength of adherence. We compare high and low MP breast cancer cells and use benign cells as a control. We monitor the time-dependent force applied by the cells to gels in a stiffness range 2-10 kPa, using traction force microscopy; applied forces are measured through cell-induced displacement of particles embedded in the gel surface. We observe that both high and low MP cancer cells apply significantly higher lateral traction forces than benign cells on stiffer gels (4.3±0.1 kPa and above), while no difference in lateral forces is observed on the softer gel (2.4±0.04 kPa). In conclusion, we have shown that there is a direct correlation between the forces applied by cancer cells and the microenvironment (gel) stiffness during the adhesion process.