title: Engineering robust and tunable spatial structures with synthetic gene circuits.
abstract: Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations. Although robust, the patterns are highly tunable, with their band widths specified by the external nisin gradient and cellular nisin immunity. Additionally, the circuits can direct cells to consistently generate designed patterns, even when the gradient is driven by structured nisin-producing bacteria and the patterning cells are composed of multiple species. A mathematical model successfully reproduces all of the observed patterns. Furthermore, the circuits allow us to establish predictable structures of synthetic communities and controllable arrays of cellular stripes and spots in space. This study offers new synthetic biology tools to program spatial structures. It also demonstrates that a deep mining of natural functionalities of living systems is a valuable route to build circuit robustness and tunability.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.|Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Wentao
authors.initials: W
authors.lastname: Kong
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.|Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Blanchard
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.|Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA luting@illinois.edu.|Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.|Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D004777:Environment; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D008954:Models, Biological; D009561:Nisin / Q000096:biosynthesis; D015398:Signal Transduction; D058615:Synthetic Biology
chemical_list: D009561:Nisin