Modeling information exchange between living and artificial cells
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The tools of synthetic biology have enabled researchers to explore multiple scientific phenomena by directly engineering signaling pathways within living cells and artificial protocells. Here, we explored the potential for engineered living cells themselves to assemble signaling pathways for non-living protocells. This analysis serves as a preliminary investigation into a potential origin of processes that may be utilized by complex living systems. Specifically, we suggest that if living cells can be engineered to direct the assembly of genetic signaling pathways from genetic biomaterials in their environment, then insight can be gained into how naturally occurring living systems might behave similarly.
To this end, we have modeled and simulated a system consisting of engineered cells that control the assembly of DNA monomers on microparticle scaffolds. These DNA monomers encode genetic circuits, and therefore, these microparticles can then be encapsulated with minimal transcription and translation systems to direct protocell phenotype. The modeled system relies on multiple previously established synthetic systems and then links these together to demonstrate system feasibility.
In this specific model, engineered cells are induced to synthesize biotin, which competes with biotinylated, circuit-encoding DNA monomers for an avidinized-microparticle scaffold. We demonstrate that multiple synthetic motifs can be controlled in this way and can be tuned by manipulating parameters such as inducer and DNA concentrations.
We expect that this system will provide insight into the origin of living systems as well as serve as a tool for engineering living cells that assemble complex biomaterials in their environment.
Keywordssynthetic biology artificial cells biotin microparticles
The authors gratefully acknowledge support from award FA9550-13-1-0108 from the Air Force Office of Scientific Research of the USA and award N00014-15-1-2502 from the Office of Naval Research of the USA. The authors additionally acknowledge support from the Institute for Critical Technology and Applied Science at Virginia Polytechnic Institute and State University, from the National Science Foundation Graduate Research Fellowship Program, award number 1607310, and from the Virginia Sea Grant Graduate Research Fellowship Program.
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