Multiplexing cell-cell communication

Mol Syst Biol. 2020 Jul;16(7):e9618. doi: 10.15252/msb.20209618.


The engineering of advanced multicellular behaviors, such as the programmed growth of biofilms or tissues, requires cells to communicate multiple aspects of physiological information. Unfortunately, few cell-cell communication systems have been developed for synthetic biology. Here, we engineer a genetically encoded channel selector device that enables a single communication system to transmit two separate intercellular conversations. Our design comprises multiplexer and demultiplexer sub-circuits constructed from a total of 12 CRISPRi-based transcriptional logic gates, an acyl homoserine lactone-based communication module, and three inducible promoters that enable small molecule control over the conversations. Experimentally parameterized mathematical models of the sub-components predict the steady state and dynamical performance of the full system. Multiplexed cell-cell communication has applications in synthetic development, metabolic engineering, and other areas requiring the coordination of multiple pathways among a community of cells.

Keywords: CRISPRi; cell-cell communication; genetic circuit design; multiplexers; synthetic biology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CRISPR-Cas Systems*
  • Cell Communication / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Escherichia coli / metabolism
  • Homoserine / genetics
  • Homoserine / metabolism
  • Metabolic Engineering / methods*
  • Promoter Regions, Genetic
  • Quorum Sensing / genetics*
  • RNA, Guide, Kinetoplastida
  • Recombinant Proteins
  • Small Molecule Libraries
  • Synthetic Biology / methods*


  • RNA, Guide
  • Recombinant Proteins
  • Small Molecule Libraries
  • Homoserine