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The interaction between the liquid and solid phases in the cytoplasm regulates the rheological behavior of cells and has a prominent role in determining how cells deform and move. In turn, the hydromechanical properties of cells, such as the viscoelastic modulus and compressibility, influence intracellular water transport, cytoskeletal-network modulation and cell-volume regulation. It is necessary to measure these properties in situ to study how cells regulate intracellular mechanics and how the properties change as cells interact with their microenvironment during aging and injury healing, as well as in the course of disease pathogenesis.