(582c) High-Frequency Microrheology in 3D Reveals Mismatch between Cytoskeletal and Extracellular Matrix Mechanics

Mechanotransduction requires that cells sense physical cues from the microenvironment and remodel both the cytoskeleton and the surrounding extracellular matrix (ECM). This dynamic interaction is thought to be crucial for healthy development and maintenance of tissue. However, the nature of the dynamic coupling remains poorly understood. Here we investigate whether cells mechanically adapt to distinct microenvironments using 3D culture models. We measured both intracellular and extracellular viscoelasticity, from five cell lines in two ECM with four cytoskeletal drug treatments at two time points of 0-4 hour and 24-28 hour. Malignant breast epithelial cells show stiffer viscoelasticity than the local ECM in 3D laminin rich ECM whereas non-malignant counterparts demonstrate similar viscoelasticity compared to the surrounding. Moreover, other breast cancer cells in tissue-mimetic hydrogels are almost four-fold stiffer than the local ECM. Perturbation of actomyosin did not yield uniform responses but instead depended on the cell type and chemistry of the hydrogel. The measured viscoelasticity of both cells and ECM is well fitted into power laws at the frequency range that controls the dynamics of cytoskeleton. Additionally, the intracellular and extracellular power law parameters from the entire data are described by two parallel master curves based on two parameters. Therefore, our works supports the hypothesis of misregulated mechanical feedback in cancer cells and further reveals potential universality in the mechanical response of these cells.