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This Podcast features an interview with Yong Ho Bae and Richard Assoian, authors of a Research Article that appears in the 17 June 2014 issue of Science Signaling, about how cells respond to the stiffness of the extracellular matrix. The stiffness of the substrate that supports a cell can determine whether the cell proliferates or becomes quiescent. Extracellular matrix stiffness naturally varies between tissues, but stiffens in areas of damage or fibrosis. Bae et al. found that fibroblasts and vascular smooth muscle cells responded to stiff substrates by stiffening their actin cytoskeletons and increasing their proliferation. The authors identified a signaling pathway that converts information about substrate stiffness into a cell proliferation trigger.