title: Coupling spatial segregation with synthetic circuits to control bacterial survival.
abstract: Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial swarmbot, which employs spatial arrangement to control the growth dynamics of engineered bacteria. As a proof of principle, we demonstrated a safeguard strategy to prevent unintended bacterial proliferation. In particular, we adopted several synthetic gene circuits to program collective survival in Escherichia coli: the engineered bacteria could only survive when present at sufficiently high population densities. When encapsulated by permeable membranes, these bacteria can sense the local environment and respond accordingly. The cells inside the microbial swarmbot capsules will survive due to their high densities. Those escaping from a capsule, however, will be killed due to a decrease in their densities. We demonstrate that this design concept is modular and readily generalizable. Our work lays the foundation for engineering integrated and programmable control of hybrid biological-material systems for diverse applications.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Anna Jisu
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Tsoi
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Feilun
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA Center for Genomic and Computational Biology, Duke University, Durham, NC, USA you@duke.edu.
authors.forename: Lingchong
authors.initials: L
authors.lastname: You
mesh_terms: D000464:Alginates / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D005818:Genetic Engineering; D056656:Lab-On-A-Chip Devices; D050296:Microbial Viability; D008958:Models, Molecular; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D049490:Systems Biology
chemical_list: D000464:Alginates; C051546:alginate-polylysine-alginate; D011107:Polylysine
keywords: collective survival; engineered bacteria; safeguard control; spatial segregation