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bioRxiv · 10.1101/2022.11.15.516470

A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design

Rajasekaran, R.·Chang, C.-C.·Weix, E. W. Z.·Galateo, T. M.·Coyle, S. M.
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Abstract

Cells self-organize molecules in space and time to generate complex behaviors, but we lack synthetic strategies for engineering spatiotemporal signaling. We present a programmable reaction-diffusion platform for designing protein oscillations, patterns, and circuits in mammalian cells using two bacterial proteins, MinD and MinE (MinDE). MinDE circuits act like "single-cell radios", emitting frequency-barcoded fluorescence signals that can be spectrally isolated and analyzed using digital signal processing tools. We define how to genetically program these signals and modulate their dynamics using engineerable protein-protein interactions. By connecting MinDE to endogenous cellular pathways, we built circuits that broadcast frequency-barcoded single-cell kinase activity or that synthetically pattern actin polymerization. Our work establishes a new paradigm for probing and engineering cellular activities at length and timescales critical for biological function.

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Rajasekaran, R., Chang, C.-C., Weix, E. W. Z., Galateo, T. M., Coyle, S. M.. 2022-11-15. A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design. https://doi.org/10.1101/2022.11.15.516470

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