Dynamic force spectroscopy on the binding of monoclonal antibodies and tau peptides

Abstract

Optical tweezers-assisted dynamic force spectroscopy (DFS) is employed to investigate specific receptor/ligand interactions on the level of single binding events. Here, the specific binding of two anti-human tau monoclonal antibodies (mAbs), HPT-110 and HPT-104, to synthetic tau-peptides with different phosphorylation patterns is analyzed. The specificity of HPT-110 to the tau-peptide containing a phosphorylation at Ser235 and of HPT-104 to the tau-peptide containing a phosphorylation at Thr231 is confirmed. Additionally, our approach allows for a detailed characterization of the unspecific interactions that are observed between HPT-104 and the peptide phosphorylated only at Ser235 and between HPT-110 and the peptide phosphorylated only at Thr231. By analyzing the measured rupture-force distributions it is possible to separate unspecific from specific interactions. Thereby for the latter characteristic parameters like the lifetime of the bond without force τ0, the characteristic length xts and the free energy of activation ΔG are determined. The results are in accordance with conventional ELISA tests but offer a much more refined insight.