Graphene field-effect transistors for sensing ion-channel coupled receptors: towards biohybrid nanoelectronics for chemical detection

Graphene field effect transistors (G-FETs) have appeared as suitable candidates for sensing charges and have thus attracted large interest for ion and chemical detections. In particular, their high sensitivity, chemical robustness, transparency and bendability offer a unique combination for interfacing living and soft matters. Here we have demonstrated their ability to sense targeted biomolecules, by combining them with ion channels-coupled receptors (ICCRs). These receptors have been naturally or artificially expressed within living cell membranes to generate ion fluxes in presence of chemicals of interest. Here, we have successfully combined those biosensors with G-FET array which converts the bio-activation of the ICCRs into readable electronic signals. This hybrid bioelectronic device leverages the advantages of the biological receptor and the graphene field effect transistor enabling the selective detection of biomolecules, which is a current shortcoming of electronic sensors. Additionally, the G-FET allows to discriminate the polarity of the ion fluxes which otherwise remains hidden from conventional electrophysiological recordings. The multisite recording ability offered by the G-FET array rises numerous possibilities for multiscale sensing and high throughput screening of cellular solutions or analytes, which is of both fundamental and applied interests in health and environment monitoring

Graphene Field‐Effect Transistors for Sensing Ion‐Channel Coupled Receptors: Toward Biohybrid Nanoelectronics for Chemical Detection

International audienceAbstract Graphene field effect transistors (G‐FETs) have appeared as suitable candidates for sensing charges and have thus attracted large interest for ion and chemical detections. In particular, their high sensitivity, chemical robustness, transparency, and bendability offer a unique combination for interfacing living and soft matters. Here demonstrated their ability to sense targeted biomolecules is demonstrated, by combining them with ion channel‐coupled receptors (ICCRs). These receptors are naturally or artificially expressed within living cell membranes to generate ion fluxes in the presence of chemicals of interest. Here, those biosensors are successfully combined with a G‐FET array which converts the bio‐activation of the ICCRs into readable electronic signals. This hybrid bioelectronic device leverages the advantages of the biological receptor and the graphene field effect transistor enabling the selective detection of biomolecules, which is a current shortcoming of electronic sensors. Additionally, the G‐FET allows for discrimination of the polarity of the ion fluxes which otherwise remains hidden from conventional electrophysiological recordings. The multisite recording ability offered by the G‐FET array raises numerous possibilities for multiscale sensing and high throughput screening of cellular solutions or analytes, which is of both fundamental and applied interest in health and environment monitoring

Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors

International audienceIn numerous insects, the olfactory receptor family forms a unique class of heteromeric cation channels. Recent progress in resolving the odorant receptor structures offers unprecedented opportunities for deciphering their molecular mechanisms of ligand recognition. Unexpectedly, these structures in apo or ligand-bound states did not reveal the pathway taken by the ligands between the extracellular space and the deep internal cavities. By combining molecular modeling with electrophysiological recordings, we identified amino acids involved in the dynamic entry pathway and the binding of VUAA1 to Drosophila melanogaster ’s odorant receptor co-receptor (Orco). Our results provide evidence for the exact location of the agonist binding site and a detailed and original mechanism of ligand translocation controlled by a network of conserved residues. These findings would explain the particularly high selectivity of Orcos for their ligands

Elucidating the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors

In numerous insects, the olfactory receptor family forms a unique class of heteromeric cation channels. Recent progress in resolving the odorant receptor structures offers unprecedented opportunities for deciphering their molecular mechanisms of ligand recognition. Unexpectedly, these structures in apo or ligand-bound states did not reveal the pathway taken by the ligands between the extracellular space and the deep internal cavities. By combining molecular modeling with electrophysiological recordings, we identified amino acids involved in the dynamic entry pathway and the binding of VUAA1 to Drosophila melanogaster ’s odorant receptor co-receptor (Orco). Our results provide new evidence for the exact location of the agonist binding site and a detailed and original mechanism of ligand translocation controlled by a network of conserved residues. These findings would explain the particularly high selectivity of Orcos for their ligands

A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions Using NMR Spectroscopy

International audienceIntrinsically disordered proteins (IDPs) are flexible biomolecules whose essential functions are defined by their dynamic nature. Nuclear magnetic resonance (NMR) spectroscopy is ideally suited to the investigation of this behavior at atomic resolution. NMR relaxation is increasingly used to detect conformational dynamics in free and bound forms of IDPs under conditions approaching physiological, although a general framework providing a quantitative interpretation of these exquisitely sensitive probes as a function of experimental conditions is still lacking. Here, measuring an extensive set of relaxation rates sampling multiple-time-scale dynamics over a broad range of crowding conditions, we develop and test an integrated analytical description that accurately portrays the motion of IDPs as a function of the intrinsic properties of the crowded molecular environment. In particular we observe a strong dependence of both short-range and long-range motional time scales of the protein on the friction of the solvent. This tight coupling between the dynamic behavior of the IDP and its environment allows us to develop analytical expressions for protein motions and NMR relaxation properties that can be accurately applied over a vast range of experimental conditions. This unified dynamic description provides new insight into the physical behavior of IDPs, extending our ability to quantitatively investigate their conformational dynamics under complex environmental conditions, and accurately predicting relaxation rates reporting on motions on time scales up to tens of nanoseconds, both in vitro and in cellulo