title: Designed cell consortia as fragrance-programmable analog-to-digital converters.
abstract: Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia. The ADC consists of multiple sampling-and-quantization modules sensing analog gaseous fragrance inputs; a gas-to-liquid transducer converting fragrance intensity into diffusible cell-to-cell signaling compounds; a digitization unit with a genetic amplifier circuit to improve the signal-to-noise ratio; and recombinase-based digital expression switches enabling 2-bit processing of logic gates. Synthetic ADCs that can remotely control cellular activities with digital precision may enable the development of novel biosensors and may provide bioelectronic interfaces synchronizing analog metabolic pathways with digital electronics.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: Marius
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Ausländer
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Spinnler
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Ausländer
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: Julian
authors.initials: J
authors.lastname: Sikorski
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Folcher
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.|Faculty of Science, University of Basel, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000703:Analog-Digital Conversion; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D009812:Odorants / Q000032:analysis*; D010476:Perfume / Q000032:analysis; D058615:Synthetic Biology / Q000379:methods*
chemical_list: D010476:Perfume