Fibrosis is a central component of numerous diseases, including liver cirrhosis, idiopathic pulmonary fibrosis, post-infarct cardiac scarring, and cancer; as such, it is implicated in an estimated 45% of all deaths in the developed world.  These diverse pathologies similarly progress toward organ failure through myofibroblast-mediated overproduction of an excessively stiff ECM.  These myofibroblasts are the very same cells that are critical to wound healing and regeneration.  What differentiates wound healing from fibrosis? What feedback signals from the microenvironment diverts a healing response toward fibrosis? Answering these questions requires a fundamental understanding of how cells sense and mechanically respond to their extracellular environs, and how this response mediates changes in ECM structure and mechanics that feedback to further propagate fibrosis.  We develop approaches that allow us to study the evolving structure and mechanical properties of fibrous ECM, while monitoring the cellular forces that drive myofibroblast signaling.  This work will shine light on biophysical mechanisms common to fibrotic changes accompanying numerous diseases, and could lead to therapies that promote regenerative healing over fibrotic scar formation.