Engineering a scalable and orthogonal platform for synthetic communication in mammalian cells.

Autor: Makri Pistikou AM; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Cremers GAO; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Nathalia BL; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Meuleman TJ; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Center for Living Technologies, Eindhoven-Wageningen-Utrecht Alliance, Utrecht, The Netherlands., Bögels BWA; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Eijkens BV; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., de Dreu A; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Bezembinder MTH; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Stassen OMJA; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Bouten CCV; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Merkx M; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Jerala R; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.; EN-FIST Centre of Excellence, Ljubljana, Slovenia., de Greef TFA; Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. t.f.a.d.greef@tue.nl.; Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. t.f.a.d.greef@tue.nl.; Computational Biology Group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. t.f.a.d.greef@tue.nl.; Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. t.f.a.d.greef@tue.nl.; Center for Living Technologies, Eindhoven-Wageningen-Utrecht Alliance, Utrecht, The Netherlands. t.f.a.d.greef@tue.nl.; Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands. t.f.a.d.greef@tue.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 02; Vol. 14 (1), pp. 7001. Date of Electronic Publication: 2023 Nov 02.
DOI: 10.1038/s41467-023-42810-5
Abstrakt: The rational design and implementation of synthetic mammalian communication systems can unravel fundamental design principles of cell communication circuits and offer a framework for engineering of designer cell consortia with potential applications in cell therapeutics. Here, we develop the foundations of an orthogonal, and scalable mammalian synthetic communication platform that exploits the programmability of synthetic receptors and selective affinity and tunability of diffusing coiled-coil peptides. Leveraging the ability of coiled-coils to exclusively bind to a cognate receptor, we demonstrate orthogonal receptor activation and Boolean logic operations at the receptor level. We show intercellular communication based on synthetic receptors and secreted multidomain coiled-coils and demonstrate a three-cell population system that can perform AND gate logic. Finally, we show CC-GEMS receptor-dependent therapeutic protein expression. Our work provides a modular and scalable framework for the engineering of complex cell consortia, with the potential to expand the aptitude of cell therapeutics and diagnostics.
(© 2023. The Author(s).)
Databáze: MEDLINE
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