Coupling ion channels to receptors for biomolecule sensing

Moreau, Christophe; Dupuis, Julien; Révilloud, Jean; Arumugam, Karthik; Vivaudou, Michel

doi:10.1038/nnano.2008.242

Cited by 59 publications

(98 citation statements)

References 27 publications

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“…One approach would be to separate the sensing and actuating functions, an idea embodied by an engineered ion channel fused with a surface receptor protein responsible for target binding (12). However, incorporating a recognition element directly on the sensor (e.g., a natural ion channel with a selectivity filter) would be another, more straightforward approach.…”

mentioning

confidence: 99%

Label-free biosensing with functionalized nanopipette probes

Umehara

Karhánek

Davis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

156

148

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Nanopipette technology can uniquely identify biomolecules such as proteins based on differences in size, shape, and electrical charge. These differences are determined by the detection of changes in ionic current as the proteins interact with the nanopipette tip coated with probe molecules. Here we show that electrostatic, biotin-streptavidin, and antibody-antigen interactions on the nanopipette tip surface affect ionic current flowing through a 50-nm pore. Highly charged polymers interacting with the glass surface modulated the rectification property of the nanopipette electrode. Affinity-based binding between the probes tethered to the surface and their target proteins caused a change in the ionic current due to a partial blockade or an altered surface charge. These findings suggest that nanopipettes functionalized with appropriate molecular recognition elements can be used as nanosensors in biomedical and biological research.biomolecules ͉ biosensor ͉ immunoassay ͉ current rectification ͉ nanopore N anopipettes, characterized by the submicron to nanoscale size of the pore at the tip, are of great interest because of their unique physicochemical properties and potential for various biomedical and biological applications. By pulling a single glass capillary, one can easily and cost-effectively create a pair of nanopipettes that can be used for molecular deposition onto a solid surface (1, 2), for delivery to the surface of a single cell (3) and its inner compartments (4, 5), or for biomolecular sensing as described hereafter. These applications can be optimized by an enhanced understanding of the physical and chemical interactions at the pore region, which has been a subject of theoretical studies (6). Advances in both technical and theoretical fronts will further demonstrate the utility of nanopipettebased devices for many purposes.Biomolecule sensing with a nanopipette probe has been performed with and without the aid of optical methods. Fluorescence-based pH sensing (7) shows the submicron spatial resolution and millisecond time resolution of such sensors. Fully-electrical detection of DNA-conjugated gold nanoparticles (8) uses resistive pulses caused by the translocation of fairly large (10 nm) particles, the underlying principle identical to that of nanopore biosensors (9) and DNA sequencers (10). Unlike other nanostructure-based chemical sensors (11), which often require access to semiconductor facilities, nanopipette biosensors can be created and tailored at the bench, thereby reducing turnaround time. Nanopipettes also have enormous potential for detecting a small number of molecules from a tiny amount of clinical samples or live single cells, a feature useful for medical diagnostics and molecular and cellular biology research.A key challenge for nanopipette biosensors is adapting to applications where specific molecules can be targeted. One approach would be to separate the sensing and actuating functions, an idea embodied by an engineered ion channel fused with a surface receptor protein responsible f...

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mentioning

confidence: 99%

Label-free biosensing with functionalized nanopipette probes

Umehara

Karhánek

Davis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

156

148

View full text Add to dashboard Cite

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“…In addition to seeking natural molecules and site-directed mutants, linking a non-light-gated ion-channel to a type I archaeal rhodopsin may be another promising approach to creating such a molecular tool (107). In this way, a light-activated shunt could be created, which would more closely mimic natural mechanisms of neural inhibition in the brain.…”

Section: Diversitymentioning

confidence: 99%

Light-Activated Ion Pumps and Channels for Temporally Precise Optical Control of Activity in Genetically Targeted Neurons

et al. 2011

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The ability to turn on and off specific cell types and neural pathways in the brain, in a temporally precise fashion, has begun to enable the ability to test the sufficiency and necessity of particular neural activity patterns, and particular neural circuits, in the generation of normal and abnormal neural computations and behaviors by the brain. Over the last 5 years, a number of naturally occurring light-activated ion pumps and light-activated ion channels have been shown, upon genetic expression in specific neuron classes, to enable the voltage (and internal ionic composition) of those neurons to be controlled by light in a temporally precise fashion, without the need for chemical cofactors. In this chapter, we review three major classes of such genetically encoded "optogenetic" microbial opsins-light-gated ion channels such as channelrhodopsins, light-driven chloride pumps such as halorhodopsins, and light-driven proton pumps such as archaerhodopsins-that are in widespread use for mediating optical activation and silencing of neurons in species from Caenorhabditis elegans to nonhuman primates. We discuss the properties of these moleculesincluding their membrane expression, conductances, photocycle properties, ion selectivity, and action spectra-as well as genetic strategies for delivering these genes to neurons in different species, and hardware for performing light delivery in a diversity of settings. In the future, these molecules not only will continue to enable cutting-edge science but may also support a new generation of optical prosthetics for treating brain disorders.

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“…To achieve a ligand-responsive nanopore, Moreau et al [70] constructed a transcriptional fusion between the GPCR (G-protein-coupled receptor) M2 and the K + channel Kir6.2 and expressed this fusion in Xenopus oocytes. Ligand binding by the GPCR induced a conformational change that was transmitted to the channel, causing it to open.…”

Section: Ligand-activated Nanoporesmentioning

confidence: 99%