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

Anna-Maria Makri Pistikou, Glenn A. O. Cremers, Bryan L. Nathalia, Theodorus J. Meuleman, Bas W. A. Bögels, Bruno V. Eijkens, Anne Dreu, Maarten T. H. Bezembinder, Oscar M. J. A. Stassen, Carlijn C. V. Bouten, Maarten Merkx, Roman Jerala and Tom F. A. Greef ()
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Anna-Maria Makri Pistikou: Eindhoven University of Technology
Glenn A. O. Cremers: Eindhoven University of Technology
Bryan L. Nathalia: Eindhoven University of Technology
Theodorus J. Meuleman: Eindhoven University of Technology
Bas W. A. Bögels: Eindhoven University of Technology
Bruno V. Eijkens: Eindhoven University of Technology
Anne Dreu: Eindhoven University of Technology
Maarten T. H. Bezembinder: Eindhoven University of Technology
Oscar M. J. A. Stassen: Eindhoven University of Technology
Carlijn C. V. Bouten: Eindhoven University of Technology
Maarten Merkx: Eindhoven University of Technology
Roman Jerala: National Institute of Chemistry
Tom F. A. Greef: Eindhoven University of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-42810-5

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