- Garibyan, Mher;
- Hoffman, Tyler;
- Makaske, Thijs;
- Do, Stephanie;
- Wu, Yifan;
- Williams, Brian;
- March, Alexander;
- Cho, Nathan;
- Pedroncelli, Nicolas;
- Lima, Ricardo;
- Soto, Jennifer;
- Jackson, Brooke;
- Santoso, Jeffrey;
- Khademhosseini, Ali;
- Thomson, Matt;
- Li, Song;
- McCain, Megan;
- Morsut, Leonardo
Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.