Abstract
The design of synthetic biology–inspired control devices enabling entire mammalian cells to receive, process and transfer metabolic information and so communicate with each other via synthetic multichannel networks may provide new insight into the organization of multicellular organisms and future clinical interventions1. Here we describe communication networks that orchestrate behavior in individual mammalian cells in response to cell-to-cell metabolic signals. We engineered sender, processor and receiver cells that interact with each other in ways that resemble natural intercellular communication networks such as multistep information processing cascades, feed-forward–based signaling loops, and two-way communication. The engineered two-way communication devices mimicking natural control systems in the development of vertebrate extremities2 and vasculature3,4,5 was used to program temporal permeability in vascular endothelial cell layers. These synthetic multicellular communication systems may inspire future therapies or tissue engineering strategies.
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Acknowledgements
We thank M. Tan (pMT1182), M. Ehrbar (pVEGF165pcDNA3), G.Y. Koh (pAng-1) and K. Frei (EA.hy926 cells) for providing reagents and D. Grasso for critical comments on the manuscript. This work was supported by the Swiss National Science Foundation (grant no. 31003A0-126022) and in part by the EC Framework 7 (Persist). Work of W.W. is supported by the Excellence Initiative of the German Federal and State Governments (EXC 294).
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W.B., M.L., W.W., J.S. and M.F. designed the project, analyzed results and wrote the manuscript. W.B. and M.D.E.-B. performed the experimental work. M.L. and J.S. designed and analyzed the mathematical model and performed the simulations.
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Supplementary Model, Supplementary Figures 1–19, Supplementary Table 1 and Supplementary Assembly (PDF 1058 kb)
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Bacchus, W., Lang, M., El-Baba, M. et al. Synthetic two-way communication between mammalian cells. Nat Biotechnol 30, 991–996 (2012). https://doi.org/10.1038/nbt.2351
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DOI: https://doi.org/10.1038/nbt.2351
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