Research ArticleSynthetic Biology

Synthetic Signal Propagation Through Direct Cell-Cell Interaction

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Science Signaling  17 Apr 2012:
Vol. 5, Issue 220, pp. ra31
DOI: 10.1126/scisignal.2002764

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Engineering Cells So That Signals Propagate

Synthetic biology can be used to reconstitute cellular processes to learn about such systems in biological contexts as well as to advance our ability to engineer systems for biomedical or environmental applications. Matsuda et al. used a cell contact–dependent feedback system based on the receptor Notch and its ligand Delta to engineer a genetic circuit that propagated a signal within a population of cultured mammalian cells. Using mathematical modeling and simulation to define the conditions that would produce the propagating signal, they found that amplification was required for signal propagation and then they engineered genetic circuits with the appropriate amplification in mammalian cultured cells. Cells with the receptor-initiated circuit were cocultured with “trigger” cells, expressing the ligand, and in the appropriately amplified system, the signal spread from the trigger cells to result in discrete groups of cells, a phenomenon that occurs in developing tissues or organs in response to Notch signaling. Not only does reconstituting patterns in cultured cells enable testing of mechanistic sufficiency of models of biological pattern formation, these results also take a step toward building genetic circuits to control endogenous signaling pathways and create cells for biomedical applications.

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