Physical Forces in Collective Motions of Cellular Aggregates

Cells in our body respond sensitively to externally applied physical forces, and cells also generate forces intracellularly. Pathological conditions such as cancer can be induced by the abnormality in the physical microenvironment, and the metastatic fate of the cells may be regulated by their physical state in the tumor mass. In this seminar, I will introduce 2D and 3D cell-based in vitro experimental models to visualize how cellular motions and stresses are correlated during aggregation and dissemination of the cellular clusters. For quantitative analyses, we utilized particle image velocimetry (PIV), traction force microscopy (TFM), and monolayer stress microscopy (MSM) along with conventional biochemical assays and other phenotyping tools. Using the simple 2D model, we unraveled the correlation between cellular kinematics and physical stresses. In the context of cancer metastasis, we first identified the active key factors that regulated the formation of the cellular aggregates and quantified the physical forces that would prevent the dissemination from the aggregates. We also developed spheroid-based 3D cancer models to investigate the invasion behavior of the cancer cells. Based on recent findings on the significance of collective migration in cancer invasion, we suggest a scaffold-based strategy as an appropriate method to form a tumor model that adequately represent the collective invasion of breast cancer cells.