Nuclei within cells are constantly subjected to compressive, tensile, and shear forces, which regulate nucleoskeletal and cytoskeletal remodeling, activate signaling pathways, and direct cell-fate decisions. Multiple rheological methods have been adapted for characterizing the response to applied forces of isolated nuclei and nuclei within intact cells. However, in vitro measurements fail to capture the viscoelastic modulation of nuclear stress-strain relationships by the physiological tethering to the surrounding cytoskeleton, extracellular matrix and cells, and tissue-level architectures.
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