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

YAP/TAZ is a master regulator of mechanotransduction whose functions rely on translocation from the cytoplasm to the nucleus in response to diverse physical cues. Substrate stiffness, substrate dimensionality, and cell shape are all input signals for YAP/TAZ, and through this pathway, regulate critical cellular functions and tissue homeostasis. Yet, the relative contributions of each biophysical signal and the mechanisms by which they synergistically regulate YAP/TAZ in realistic tissue microenvironments that provide multiplexed input signals remain unclear.

Emerging themes and unifying concepts underlying cell behavior regulation by the pericellular space.

Cells reside in a complex three-dimensional (3D) microenvironment where physical, chemical, and architectural features of the pericellular space regulate important cellular functions like migration, differentiation, and morphogenesis. A major goal of tissue engineering is to identify which properties of the pericellular space orchestrate these emergent cell behaviors and how. In this review, we highlight recent studies at the interface of biomaterials and single cell biophysics that are lending deeper insight towards this goal.