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Length and time scales of cell-cell signaling circuits in agar

Doong, Joy and Parkin, James and Murray, Richard M. (2017) Length and time scales of cell-cell signaling circuits in agar. . (Unpublished)

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A community of genetically heterogeneous cells embedded in an unmixed medium allows for sophisticated operations by retaining spatial differentiation and coordinating division-of-labor. To establish the principles of engineering reliable cell-cell communication in a heterogeneous environment, we examined how circuit parameters and spatial placement affect the range of length and time scales over which simple communication circuits interact. We constructed several "sender" and "receiver" strains with quorum-sensing signaling circuits. The sender cell colony produces acyl homoserine lactones (AHL), which diffuse across the semisolid medium. The receiver cell colony detects these signal molecules and reports by fluorescence. We have found that a single colony of one sender variant is sufficient to induce receiver response at more than 1.5cm separation. Furthermore, AHL degradase expression in receiver colonies produces a signal threshold effect and reduces the response level in subsequent receiver colonies. Finally, our investigation on the spatial placement of colonies gave rise to the design of a multicellular long-range communication array consisting of two alternating colony types. Its signal response successfully propagated colony-by-colony along a six-colony array spanning 4.8cm at a transmission velocity of 12.8 hours per colony or 0.075cm per hour. In addition, we have developed a reaction-diffusion model that recreates the observed behaviors of the many performed experiments using data-informed parameter estimates of signal diffusion, gene expression, and nutrient consumption. These results demonstrate that a mixed community of colonies can enable new patterning programs, and the corresponding model will facilitate the rational design of complex communication networks.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Doong, Joy0000-0001-8987-6903
Parkin, James0000-0002-4058-2338
Murray, Richard M.0000-0002-5785-7481
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. bioRxiv preprint first posted online Nov. 18, 2017. We thank Andrey Shur for technical assistance with the microscope, Shan Huang for sharing E. coli stock and other Murray Lab members for useful discussions. Joy Doong was supported by the Amgen Scholar Program and James M. Parkin is supported by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Plasmid vectors and non-coding regions were provided by Douglas Densmore at the Cross-disciplinary Integration of Design Automation Research lab (Addgene Kit # 1000000059). Quorum sensing promoters, coding sequences and CY026 strain were provided by Matthew Bennett (Addgene Plasmid # 65954, 65952, 72340).
Funding AgencyGrant Number
AmGen Scholars ProgramUNSPECIFIED
Army Research Office (ARO)W911NF-09-0001
Record Number:CaltechAUTHORS:20181031-100811065
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Official Citation:Length and time scales of cell-cell signaling circuits in agar. Joy Doong, James Parkin, Richard M. Murray. bioRxiv 220244; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90541
Deposited By: Tony Diaz
Deposited On:01 Nov 2018 17:57
Last Modified:01 Nov 2018 17:57

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