Dynamic changes in cellular mechanics and membrane microviscosity during migration of colorectal cancer cells.

The ability of tumor cells to migrate and invade adjacent tissue is a key property underlying the metastatic process. To ensure greater deformability and to facilitate movement, migratory cells undergo multiple changes in biophysical parameters, including those of stiffness and membrane viscosity. However, reports on correlations between cell motility and stiffness, or between cell motility and membrane microviscosity are rather limited and conflicting. Here, using atomic force microscopy (AFM) and fluorescence lifetime imaging (FLIM), we have investigated alterations in the mechanical properties of cancer cells and in the microviscosity of their plasma membranes that are associated with the migration process. It was found that upon activation of migration either through a "wound healing" test or by inducing epithelial-mesenchymal transition, human colorectal cancer cells undergo profound biomechanical remodeling characterized by simultaneous decreases in cell stiffness and in plasma membrane microviscosity. Our findings, therefore, support the results of previous studies that have shown cell softening and membrane fluidization to be critical adaptive responses enabling cell movement and that these can be regarded as potential biomarkers of tumor cell motility, offering scope for identifying new therapeutic targets.