Ligand discrimination in hOR1A1 based on the capacitive response

The mechanisms of odor discrimination are based on the differential interactions of odorant molecules with olfactory receptors (ORs). The biohybrid sensors described so far using ORs show selectivity towards specific versus non-specific binding. Here we disclose a method that enables odorant discrimination based on modulation of the capacitive response of the receptor that allows differentiation of three high-affinity hOR1A1 agonists. We performed voltammetry and impedance measurements of the hOR1A1 receptor selectively immobilized on a gold electrode in the absence and presence of the agonists. Binding induces a decrease in the capacitive response of the receptor that is proportional to the ligand affinity, and which is attributed to changes in the magnitude and orientation of the electric dipole in the receptor, regulating its response to the applied electric field.