YAP is a key mechanotransduction protein with essential roles in diverse physiological
processes. Dysregulation in YAP activity is associated with multiple diseases such as
atherosclerosis, fibrosis, and cancer progression. Here we examine the physical stimuli that
regulate dynamic YAP translocation to the nucleus. Through a combination of biophysical
studies, we demonstrate that YAP localization is insensitive to cell substrate stiffness, but
strongly determined by cellular contractile work, which in turn deforms the nucleus. We show …