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.

Details

Title
Autonomous bacterial localization and gene expression based on nearby cell receptor density
Author
Hsuan-Chen, Wu 1 ; Chen-Yu, Tsao 1 ; Quan, David N 1 ; Cheng, Yi 2 ; Servinsky, Matthew D 3 ; Carter, Karen K 4 ; Jee, Kathleen J 5 ; Terrell, Jessica L 1 ; Zargar, Amin 4 ; Rubloff, Gary W 2 ; Payne, Gregory F 1 ; Valdes, James J 6 ; Bentley, William E 7 

 Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD, USA 
 Department of Material Science and Engineering, University of Maryland, College Park, MD, USA 
 Sensors and Electron Devices Directorate, US Army Research Laboratory, Adelphi, MD, USA 
 Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD, USA; Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA 
 Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA 
 US Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD, USA 
 Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD, USA; Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA 
Section
Article
Publication year
2013
Publication date
2013
Publisher
EMBO Press
e-ISSN
17444292
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2299135052
Copyright
© 2013. This work is published under http://creativecommons.org/licenses/by-nc-sa/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.