Ligand discrimination in hOR1A1 based on the capacitive response

Area of Science:

• Biophysics
• Sensory Neuroscience
• Analytical Chemistry

Background:

• Odorant discrimination relies on differential interactions between odorant molecules and olfactory receptors (ORs).
• Existing biohybrid sensors lack the ability to differentiate between odorants with varying affinities for the same receptor.
• This limitation hinders precise odor detection and analysis.

Purpose of the Study:

• To develop a new method for odorant discrimination based on the modulation of olfactory receptor capacitive response.
• To demonstrate the differentiation of high-affinity agonists for the human olfactory receptor 1A1 (hOR1A1).

Main Methods:

• Selective immobilization of the hOR1A1 receptor on a gold electrode.
• Voltammetry and impedance measurements were performed in the presence and absence of odorant agonists.
• Analysis of the capacitive response changes induced by ligand binding.

Main Results:

• Odorant binding to hOR1A1 induced a decrease in the receptor's capacitive response.
• The magnitude of this decrease was proportional to the ligand's binding potency.
• A significant decrease (up to 40%) was observed for the cognate ligand, dihydrojasmone.
• This modulation is attributed to alterations in the receptor's electric dipole moment and its interaction with the electric field.

Conclusions:

• The developed method enables odorant discrimination by measuring changes in receptor capacitive response.
• This approach allows for the differentiation of ligands based on their binding affinity to olfactory receptors.
• This technique offers a new paradigm for developing advanced olfactory sensors with enhanced specificity.