13C-isotope-editing of nanoscale infrared images reveals the action of an inhibi­tory peptide against amyloid-β aggregation

Interactions between molecules are fundamental in biology. They occur also between amyloidogenic polypeptides that are associated with different amyloid diseases, which makes it important to study their interactions. However, addressing such research questions with imaging techniques is hindered by the problem to distinguish different polypeptides without adding artificial probes for detection. Here we present a new method for this purpose. We show that 13C-labeling can be used to distinguish peptides in nanoscale images of their infrared absorption, even when they have similar secondary structure. We studied different aggregation states of the amyloid-β peptide (Aβ) and its interaction with an inhibitory cell-penetrating peptide (NCAM1-PrP) using scattering-type scanning near field microscopy. Labeled and unlabeled peptides could be discriminated by comparing images of the optical phase taken at wavenumbers characteristic for either the labeled or the unlabeled peptide. NCAM1-PrP seems to be able to dissolve or coat existing Aβ fibrils because "naked" Aβ fibrils are not detected after mixing.