Publications

Odorant discrimination mechanisms are based on the differential interactions between odorant molecules and olfactory receptors (ORs). Biohybrid sensors based on ORs described to date show selectivity towards specific versus non-specific binding of odorants, being unable to distinguish between specific ligands of different affinity. Here we disclose a method that enables odorant discrimination based on the modulation of the capacitive response of the receptor, which allows the 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 potency, reaching up to a 40% decrease for the cognate ligand dihydrojasmone, which is attributed to changes in the magnitude and orientation of the electric dipole in the receptor, thereby regulating its response to the applied electric field.

JTD Keywords: Agonist, Biosenso, Electric dipol, Electrochemical impedance spectroscopy, Impedance, Nose, Odorant receptors, Olfactory receptor, Selectivity, Specific capacitance

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ~ 2–4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.

JTD Keywords: Atomic force microscopy, Atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, capsid protein, DNA, double stranded DNA, amino acid composition, article, atomic force microscopy, bacteriophage, bacteriophage T7, dielectric constant, dipole, DNA binding, DNA packaging, DNA structure, electron microscopy, ligand binding, nonhuman, polarization, priority journal, protein analysis, protein DNA interaction, scanning probe microscopy, static electricity, virion, virus capsid, virus particle, atomic force microscopy, atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, Bacteriophage T7, Capsid, Cations, Dielectric Spectroscopy, DNA, DNA, Viral, DNA-Binding Proteins, Electrochemical Techniques, Ligands, Microscopy, Atomic Force, Models, Chemical, Nuclear Proteins