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

Autor: Mher Garibyan, Tyler Hoffman, Thijs Makaske, Stephanie K. Do, Yifan Wu, Brian A. Williams, Alexander R. March, Nathan Cho, Nicolas Pedroncelli, Ricardo Espinosa Lima, Jennifer Soto, Brooke Jackson, Jeffrey W. Santoso, Ali Khademhosseini, Matt Thomson, Song Li, Megan L. McCain, Leonardo Morsut
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-21 (2024)
Druh dokumentu: article
ISSN: 2041-1723
52332128
DOI: 10.1038/s41467-024-50126-1
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz: