Odorant Binding Changes the Electrical Properties of Olfactory Receptors at the Nanoscale

International audienceOlfactory receptors (ORs) comprise the largest multigene family in the vertebrates. They belong to the class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins, having widespread, significant roles in signal transduction in cells, and therefore, they are a major pharmacological target. Moreover, ORs displayed high selectivity and sensitivity towards odorant detection, a characteristic that raised the interest for developing biohybrid sensors based on ORs for the detection of volatile compounds. The transduction of odorant binding into cellular signaling by ORs is not well understood and knowing its mechanism would enable developing new pharmacology and high performance biohybrid electronic sensors. Recent findings suggest that ligand recognition by ORs is determined by the nanoscale alterations of charge distribution in the receptor structure (Ref). However, the electrical characterization of ORs and their response towards ligand binding in bulk experiments is subjected to microscopic models and assumptions [2]. Here, we have directly determined the nanoscale electrical properties of ORs with unprecedented control over the receptor orientation, and their change upon odorant binding, using electrochemical scanning tunneling microscopy (EC-STM) in near-physiological conditions. Recordings of current versus time, distance, and electrochemical potential allows determining the OR impedance parameters and their dependence with odorant binding. The simultaneous measurement of RC equivalent by means of the open-circuit voltage (VOC) allows increasing the electrical sensitivity at the single receptor level for biosensing applications. Our results allow validating OR structural-electrostatic models and their functional activation processes