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Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology is unknown. Using gain- and loss-of-function approaches, we show that tumor necrosis factor-α (TNFα)-induced inflammation alters cell morphology and biophysical properties (circularity, contractility, cell stiffness, and hydraulic permeabilit