YAP/TAZ nucleocytoplasmic shuttling is a fundamental readout of cellular mechanotransduction. This pathway is critical for understanding responses to factors in the cellular microenvironment and more recently has also been shown to influence cellular circadian clocks. There are many factors that can affect this mechanotransduction including cell and nuclear shape, local curvature and culture conditions including 2D and 3D substrate presentation. Recently, this process has been studied using computational modeling to explore different mechanical and chemical conditions that regulate YAP/TAZ nuclear mechanotransduction. In this talk, I will briefly summarize some of the issues of substrate dimensionality and crosstalk between local curvature and YAP/TAZ translocation on flat surfaces versus nanopillar substrates. I will then show how nuclear deformation and rupture can regulate such mechanotransduction activities.