A spatial model of YAP/TAZ signaling reveals how stiffness, dimensionality, and shape contribute to emergent outcomes

Significance The YAP/TAZ pathway plays a fundamental role in integrating a variety of cellular cues to control important physiological processes. Here, we develop a spatial model of this pathway that contributes quantitative understanding and disentangles the role various stimuli play that are difficult to distinguish experimentally. The model integrates key spatial and physical inputs, namely cell and nuclear shape, surface area-to-volume ratios of cytoplasmic and nuclear compartments, substrate dimensionality, substrate activation area, and substrate stiffness, through membrane-proximal, cytoskeletal, and nuclear mechanotransduction modules. The resulting model accounts for seemingly contradictory experimental trends and lends new insight into controlling YAP/TAZ signaling.