PT  - JOURNAL ARTICLE
AU  - Rohith Rajasekaran
AU  - Chih-Chia Chang
AU  - Elliott W. Z. Weix
AU  - Thomas M. Galateo
AU  - Scott M. Coyle
TI  - A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design
AID  - 10.1101/2022.11.15.516470
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.15.516470
4099  - http://biorxiv.org/content/early/2022/11/27/2022.11.15.516470.short
4100  - http://biorxiv.org/content/early/2022/11/27/2022.11.15.516470.full
AB  - 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.Competing Interest StatementA provisional patent application has been filed by the University of Wisconsin and the Wisconsin Alumni Research Foundation related to this work.