Cell stiffness is an important characteristic of cells and their response to external stimuli. In this review, we survey methods used to measure cell stiffness, summarize stimuli that alter cell stiffness, and discuss signaling pathways and mechanisms that control cell stiffness. Several pathological states are characterized by changes in cell stiffness, suggesting this property can serve as a potential diagnostic marker or therapeutic target. Therefore, we consider the effect of cell stiffness on signaling and growth processes required for homeostasis and dysfunction in healthy and pathological states. Specifically, the composition and structure of the cell membrane and cytoskeleton are major determinants of cell stiffness, and studies have identified signaling pathways that affect cytoskeletal dynamics both directly and by altered gene expression. We present the results of studies interrogating the effects of biophysical and biochemical stimuli on the cytoskeleton and other cellular components and how these factors determine the stiffness of both individual cells and multicellular structures. Overall, these studies represent an intersection of the fields of polymer physics, protein biochemistry, and mechanics, and identify specific mechanisms involved in mediating cell stiffness that can serve as therapeutic targets.

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