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Electronic modulation of biochemical signal generation



Microelectronic devices that contain biological components are typically used to interrogate biology1,2 rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering3,4,5,6,7, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled8 on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip9 and could be used to revolutionize drug development10. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems11,12 and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

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Figure 1: Schematic of the biohybrid device controlled by electronic signals.
Figure 2: Electronically driven HLPT attenuation by natural mediator acetosyringone (AS).
Figure 3: On-chip enzyme activity is linear with input charge.
Figure 4: In situ enzyme attenuation mediates biological signalling.


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The authors thank the UMD Fischell Department of Bioengineering Core FACS Facility for assistance with FACS data collection and the UMD Nanocenter for providing workspace and tools for electrode fabrication and ICP-EOS measurements. The authors thank Y. Zhou of the UMD Department of Nutrition and Food Science for help with EPR measurements. Financial support for this work was provided by the Defense Threat Reduction Agency (HDTRA1-13-0037), the National Science Foundation (no. 1160005 to WEB, no. 1264509 to HO Sintim) and the RWD Foundation.

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T.G., E.K., G.F.P. and W.E.B. developed the concepts and planned and designed the experiments. T.G., E.K., H.B. and Y.C. fabricated components and performed the experiments and data analysis. J.J.Y., G.F.P., W.E.B. and G.R. supervised the work. T.G., E.K., G.F.P. and W.E.B. wrote and edited the manuscript.

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Correspondence to William E. Bentley.

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The authors declare no competing financial interests.

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Gordonov, T., Kim, E., Cheng, Y. et al. Electronic modulation of biochemical signal generation. Nature Nanotech 9, 605–610 (2014).

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