How do cells stiffen?

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 stiff-ness. Several pathological states are characterized by changes in cell stiffness, suggest-ing 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 determi-nants of cell stiffness, and studies have identified signaling pathways that affect cytoskel-etal dynamics both directly and by altered gene expression. We present the results of studies interrogating the effects of biophysical and biochemical stimuli on the cytoskel-eton and other cellular components and how these factors determine the stiffness of both individual cells and multicellular structures. Overall, these studies represent an inter-section of the fields of polymer physics, protein biochemistry, and mechanics, and iden-tify specific mechanisms involved in mediating cell stiffness that can serve as therapeutic targets.