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Garibyan, Mher; Hoffman, Tyler; Makaske, Thijs; Do, Stephanie K; Wu, Yifan; Williams, Brian A; March, Alexander R; Cho, Nathan; Pedroncelli, Nicolas; Lima, Ricardo Espinosa; et al (, Nature Communications)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.more » « less
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Lam, Calvin; Saluja, Sajeev; Courcoubetis, George; Yu, Dottie; Chung, Christian; Courte, Josquin; Morsut, Leonardo (, ACS Synthetic Biology)
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Liu, Allen P.; Appel, Eric A.; Ashby, Paul D.; Baker, Brendon M.; Franco, Elisa; Gu, Luo; Haynes, Karmella; Joshi, Neel S.; Kloxin, April M.; Kouwer, Paul H.; et al (, Nature Materials)
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