Autonomous bacterial localization and gene expression based on nearby cell receptor density |
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| Authors: | Hsuan‐Chen Wu Chen‐Yu Tsao David N Quan Yi Cheng Matthew D Servinsky Karen K Carter Kathleen J Jee Jessica L Terrell Amin Zargar Gary W Rubloff Gregory F Payne James J Valdes William E Bentley |
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| Affiliation: | 1. Fischell Department of Bioengineering, University of Maryland, , College Park, MD, USA;2. Institute for Bioscience and Biotechnology Research, University of Maryland, , College Park, MD, USA;3. Department of Material Science and Engineering, University of Maryland, , College Park, MD, USA;4. Sensors and Electron Devices Directorate, US Army Research Laboratory, , Adelphi, MD, USA;5. Department of Chemical and Biomolecular Engineering, University of Maryland, , College Park, MD, USA;6. US Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, , MD, USA |
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| Abstract: | Escherichia coli were genetically modified to enable programmed motility, sensing, and actuation based on the density of features on nearby surfaces. Then, based on calculated feature density, these cells expressed marker proteins to indicate phenotypic response. Specifically, site‐specific synthesis of bacterial quorum sensing autoinducer‐2 (AI‐2) is used to initiate and recruit motile cells. In our model system, we rewired E. coli's AI‐2 signaling pathway to direct bacteria to a squamous cancer cell line of head and neck (SCCHN), where they initiate synthesis of a reporter (drug surrogate) based on a threshold density of epidermal growth factor receptor (EGFR). This represents a new type of controller for targeted drug delivery as actuation (synthesis and delivery) depends on a receptor density marking the diseased cell. The ability to survey local surfaces and initiate gene expression based on feature density represents a new area‐based switch in synthetic biology that will find use beyond the proposed cancer model here. |
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| Keywords: | cancer EGFR Escherichia coli quorum sensing synthetic biology |
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