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Tuesday September 09 2008

Biomimetic nanotechnology: a new family of biosensors

CEA
Researchers at the Jean-Pierre Ebel Institute of Structural Biology[1] (CEA-CNRS-UJF) and the Institute of life sciences research and technologies[2] (CEA) have finalized the development of a new generation of biosensors[3]. Protein engineering has enabled them to create proteins that combine two functions: recognizing chemical signals and transducing these signals into electrical signals. These next-generation biosensors could pave the way to miniaturized detection systems that can be used for screening therapeutic targets, for diagnostics, or for detecting toxins. This research has just been published in Nature Nanotechnology.


As custom-tailored therapy begins to make it mark, biological analysis is about to leave the lab and re-establish itself at the foot of hospital beds. Biotech research is therefore increasingly geared towards developing breakthrough nanotechnologies that will make it quick and easy to pinpoint specific information. In order to develop more powerful biosensors, the IBS team focused on the proteins that regulate cell-cell signal transmission. Since the cell is enveloped in a selectively-permeable lipid membrane, role-specialized membrane proteins are required to carry substances or messages through. Their receptors identify chemical signals stemming from other cells or from the environment, while ion channels look after transferring the ions responsible for generating electrical signals.
What the researchers did was to artificially engineer proteins coupling receptors and ion channels. Christened ICCR (Ion Channel-Coupled Receptors), these nano-objects are only 10 nm wide but are able to detect biological molecules (hormones, neurotransmitters) via their receptor component while inducing an electrical signal via their ion channel component. This enables these biosensors to detect and signal the presence of even the tiniest quantity of molecules. The ability of these ICCR to directly generate an electrical signal is a key advantage for integration into miniaturized electronic systems.
The research team started by designing biosensors for two major pharmacological target molecules as a stepping stone towards developing screening tests for new medical target molecules. However, the path is now open to develop in vitro diagnostic testing or for detecting toxic agents.This research, which was conducted within the framework of the European Receptronics[4] project (www.receptronics.org), represents one of the pioneers successes in biomimetics-driven nanotech applications.

ICCRs (Ion Channel-Coupled Receptors): how they work
In an ICCR, the receptor is bound to an ion channel to create a strong mechanical bond between the two proteins. When the receptor detects, say, molecule X, it undergoes a structural change that is directly transmitted to the channel. This will have repercussions on the level to which the channel is open, and thus on the volume of ion transport through the channel. This ion flow is fairly straightforward to measure as an electrical current.

 
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Article reference:
Moreau CJ, Dupuis JP, Revilloud J, Arumugam K, Vivaudou M (2008) Coupling ion channels to receptors for biomolecule sensing. Nature Nanotech. in press.
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Research teams – references:
Membrane proteins laboratory, J.P. Ebel Institute of Structural Biology/CEA - CNRS - Joseph Fourier University, 41, rue Jules Horowitz, F-38027 GRENOBLE Cedex 1


[1]IBS: A CEA-CNRS-Joseph Fourier University of Grenoble joint-run institute
[2] IRTSV: CEA Institute, Grenoble
[3] Biosensor: a system capable of identifying and highlighting the presence of a biological molecule in the environment.
[4] Receptronics: A European research area project launched as part of the FP6 program under the nanotechnologies and nanosciences thematic priority, with the objective of syndicating biology, nanotechnology and microelectronics to create ultrasensitive miniaturized biomolecular detection systems.