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Ligand discrimination in hOR1A1 based on the capacitive response.

Anna Lagunas1, Christine Belloir2, Maxence Lalis3

  • 1CIBER-BBN, ISCIII, Madrid, Spain; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology, C/Baldiri i Reixac 10-12, 08028, Barcelona, Spain.

Biosensors & Bioelectronics
|December 3, 2024
PubMed
Summary

This study introduces a novel method for distinguishing between odorants using olfactory receptors (ORs) by measuring changes in their electrical properties. This advancement allows for the differentiation of specific odorant molecules based on their binding affinity.

Keywords:
AgonistElectric dipoleImpedanceOlfactory receptorSelectivitySpecific capacitance

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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.