Publications
Nature communicationsJul 2024 |
15
(
1
),
5891
DOI:
10.1038/s41467-024-50126-1

Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs

Garibyan, Mher; Hoffman, Tyler; Makaske, Thijs; Do, Stephanie K; Wu, Yifan; Williams, Brian A; March, Alexander R; Cho, Nathan; Pedroncelli, Nicolas; Lima, Ricardo Espinosa; Soto, Jennifer; Jackson, Brooke; Santoso, Jeffrey W; Khademhosseini, Ali; Thomson, Matt; Li, Song; McCain, Megan L; Morsut, Leonardo
Product Used
Genes
Abstract
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.
Product Used
Genes

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