Probing the role of tissue biophysics in metastasis*

Tissue homeostasis and malignant transformation are modulated by the reciprocal crosstalk between cells and the surrounding extracellular matrix (ECM), which encompasses both long-term matrix organization and short-term biochemical responses. I will present data obtained using broad band optical trap- active microrheology to probe the microscale rigidity and viscoelasticity at locations inside the cell cytoplasm and in the surrounding 3D ECM. These measurements were acquired with near simultaneity and at high frequencies relevant to molecular dynamics. A mechanical mismatch wherein the tumor cells are more rigid than the surrounding ECM was observed. In the frequency regime about the terminal relaxation time, both intracellular and extracellular measurements of the microscale rigidity relate to oscillation frequency by monomial power laws in the range 400 Hz – 15 kHz independent of type of matrix and perturbation of the cytoskeletal dynamics. These data also extend the frequency range revealing a stronger power law dependence for both intracellular and the coupled extracellular mechanics. The exponents and coefficients of these power laws are anti-correlated and collapse onto master curves. These data suggest that there is a mismatch between cells and the ECM when cells are cultured in 3D mimetics in the frequency range at which single filament dynamics emerge.