Complex tissue models aim to recapitulate features of native tissues to model development, disease pathogenesis, and drug treatments. While techniques have been developed to improve the complexity of engineered tissues, it remains challenging to coordinate and spatially control multicellular phenotypes during differentiation processes. The work presented in this thesis describes the coordinated development of engineered cells and materials to enable communication via synthetic notch receptor pathways to control multi-fate differentiation. First, I will highlight the need to incorporate synthetic biology techniques to improve complex tissue engineering. Next, I will demonstrate the methods of engineering cells with synthetic pathways. Following, I will describe the development of a library of synthetic ligand-presenting material substrates with capacity to spatially activate synthetic pathways in 2D and 3D microenvironments. In the next chapter, I summarize how we utilize ligand-patterned substrates to spatially control myogenic and endothelial differentiation in the same culture. Subsequently, I detail our investigations into how substrate mechanical properties influence activation of synthetic receptors. Finally, I present the fabrication of a RNAi dual-gradient hydrogel for interfacial gene silencing of encapsulated cells. This work contributes to improving the complexity of tissue models and therapeutics by enabling engineered microenvironments to directly influence gene expression and control cell phenotypes.