Label-free detection and characterization of the binding of hemagglutinin protein and broadly neutralizing monoclonal antibodies using terahertz spectroscopy

Abstract

Hemagglutinin (HA) is the main surface glycoprotein of the influenza A virus. The H9N2 subtype influenza A virus is recognized as the most possible pandemic strain as it has crossed the species barrier, infecting swine and humans. We use terahertz spectroscopy to study the hydration shell formation around H9 subtype influenza A virus's HA protein (H9 HA) as well as the detection of antigen binding of H9 HA with the broadly neutralizing monoclonal antibody. We observe a remarkable concentration dependent nonlinear response of the H9 HA, which reveals the formation process of the hydration shell around H9 HA molecules. Furthermore, we show that terahertz dielectric properties of the H9 HA are strongly affected by the presence of the monoclonal antibody F10 and that the terahertz dielectric loss tangent can be used to detect the antibody binding at lower concentrations than the standard ELISA test.

Label-free sensing of the binding state of MUC1 peptide and anti-MUC1 aptamer solution in fluidic chip by terahertz spectroscopy

“…5, we can confirm that the absorption variation originates from the binding-induced change of the hydrogen bond network in and around the aptamer-peptide complex. This tendency of biomolecular interaction inducing the decrease of THz absorption coefficients of corresponding solutions, is consistent with previous reports [27,39]. Furthermore, we see in Fig.…”

“…Meaningful molecular details for MUC1 peptide and aptamer binding were successfully obtained by molecular dynamics (MD) simulation, which showed the number of hydrogen bonds in and around the aptamer changed with the binding process [26]. On account of hydration shell alteration, the binding reaction of hemagglutinin (HA) subtypes H9 with a human HA-specific neutralizing monoclonal antibody F10 was detected by THz spectroscopy [27]. These findings provide motivation for further investigation into a more promising binding reaction, the MUC1 peptide and anti-MUC1 aptamer, by THz spectroscopy to meet the demand of label-free detection and the SELEX methodology.…”

Determination of Critical Micelle Concentrations of Surfactants by Terahertz Time-Domain Spectroscopy

“…At THz frequencies, the hydration water has higher absorption coefficient comparing to bulk water [47]; therefore, the total absorption coefficient increases with the increase of the concentration after the intersection. The variation trend of the absorption coefficient with the concentration for the surfactant solution is similar to the hemagglutinin protein solution before the occurrence of the overlapping of the hydration shells [40] and the peptides solution at 79 K [42] in spite of the difference in structure between surfactants and the protein or peptide biomolecules. Since the occurrences of CMC and the formation of micelles are related to the hydration process of the surfactants, the size of the hydration shell of the micelle is an interesting concern.…”

Terahertz Spectroscopy Applied to Diagnostics in Public Health: A Review

“…HA is the main surface glycoprotein of influenza A virus, which of subtype H9N2 has been recognized as the most likely pandemic strain, crossing host species barrier and infecting swine and human beings. The THz spectroscopy has been applied to assess the formation of hydration layer around the protein HA of virus [40].…”