Ligand discrimination in hOR1A1 based on the capacitive response

12 August 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

Selectivity
Olfactory receptor
Agonist
Impedance
Specific capacitance
Electric dipole

Supplementary materials

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Supplementary Information
Description
Containing: Functional tests of the hOR1A1-transfected HEK293 cells using the cAMP-mediated luciferase assay (GloSensor assay), Specific capacitance (Cs) obtained from voltammetry, PEIS data at zero polarization, Brug's equation, CPE parameters obtained from the fitting of PEIS spectra at zero polarization, and calculated Cs from Brug’s equation, PEIS of polarization experiments, CPE parameters obtained from the fitting of PEIS spectra at +150 mV polarization, and calculated Cs from Brug’s equation, equations for the imaginary part of the complex capacitance and the relaxation time constant, KDE plots showing the distribution of dipole moment magnitudes and the distribution of the dipole moment vector deviation from the z-axis for the active and inactive conformation of hOR1A1 with and without N and C-terminal tags, KDE plots for dipole moment magnitudes and dipole moment vector deviation comparing hOR1A1 to other GPCRs.
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