Coupling of perinuclear actin cap and nuclear mechanics regulates flow-induced YAP spatiotemporal nucleocytoplasmic transport

Flow shear stress controls fundamental behaviors of cells. It can modulate nuclear mechanotransduction through regulating the transport of transcriptional activators such as Yes-associated protein (YAP) from cytoplasm to nucleus. However, the mechanism how flow induces the nucleocytoplasmic transport remains largely unclear. Here we show that flow applied to endothelial cells not only drives polarized actin reorganization but also alters nuclear mechanics, which synergically controls nuclear deformation, resulting in YAP nucleocytoplasmic transport through combination of biological experiments and mechanochemical models. We discovered that unidirectional flow induces simultaneous actin caps formation and nuclear stiffening in a dose and timing-dependent manner, which causes YAP initially entering the nucleus, but then gradually exporting. Additionally, pathological oscillatory flow affects the mechanotransduction by forming slight actin cap and softening nucleus, which sustains YAP nuclear localization. Our work unveils a mechanism of flow-induced nucleocytoplasmic transport, which potentially provides a universal linkage between transcriptional regulation and mechanical stimulation.