Probing of various physiologically relevant metals-amyloid-β peptide interactions with a lipid membrane-immobilized protein nanopore [corrected].

One of the prevailing paradigms regarding the onset of Alzheimer's disease endows metal ions with key roles in certain steps of the amyloid-β (Aβ) peptide aggregation cascade, through peptide conformational changes induced by metal binding. Herein, we focused on the truncated, more soluble Aβ1-16 peptide fragment from the human Aβ1-40, and demonstrated the utility of a sensing element based on the α-hemolysin (α-HL) protein to examine and compare at single-molecule level the interactions between such peptides and various metals. By using the same approach, we quantified Cu(2+) and Zn(2+) binding affinities to the Aβ1-16 fragment, whereas the statistical analysis of blockages induced by a single Aβ1-16 peptide on the current flow through an open α-HL pore show that the metal propensity to interacting with the peptide and entailing conformational changes obey the following order: Cu(2+) > Zn(2+) > Fe(3+) > Al(3+).