EMT changes actin cortex rheology in a cell-cycle-dependent manner.

The actin cortex is a key structure for cellular mechanics and cellular migration. Accordingly, cancer cells were shown to change their actin cytoskeleton and their mechanical properties in correlation with different degrees of malignancy and metastatic potential. Epithelial-mesenchymal transition (EMT) is a cellular transformation associated with cancer progression and malignancy. To date, a detailed study of the effects of EMT on the frequency-dependent viscoelastic mechanics of the actin cortex is still lacking. In this work, we have used an established atomic force microscope-based method of cell confinement to quantify the rheology of the actin cortex of human breast, lung, and prostate epithelial cells before and after EMT in a frequency range of 0.02-2 Hz. Interestingly, we find for all cell lines opposite EMT-induced changes in interphase and mitosis; whereas the actin cortex softens upon EMT in interphase, the cortex stiffens in mitosis. Our rheological data can be accounted for by a rheological model with a characteristic timescale of slowest relaxation. In conclusion, our study discloses a consistent rheological trend induced by EMT in human cells of diverse tissue origin, reflecting major structural changes of the actin cytoskeleton upon EMT.