Recent evidence shows that metal coordination by amyloid beta peptides (A beta) determines structural alterations of peptides, and His-13 from A beta is crucial for Cu2+ binding. This study used the truncated, more soluble A beta(1-16) isoforms derived from human and rat amyloid peptides to explore their interaction with Cu2+ by employing the membrane-immobilized alpha-hemolysin (alpha-HL) protein as a nanoscopic probe in conjunction with single-molecule electrophysiology techniques. Unexpectedly, the experimental data suggest that unlike the case of the human A beta(1-16) peptide, Cu2+ complexation by its rat counterpart leads to an augmented association and dissociation kinetics of the peptide reversible interaction with the protein pore, as compared to the Cu2+-free peptide. Single-molecule electrophysiology data reveal that both human and rat Cu2+-complexed A beta peptides induce a higher degree of current flow obstruction through the alpha-HL pore, as compared to the Cu2+-free peptides. It is suggested that morphology changes brought by Cu2+ binding to such amyloidic fragments depend crucially upon the presence of the His-13 residue on the primary sequence of such peptide fragments, and the alpha-HL protein-based approach provides unique opportunities and challenges to probing metal-induced folding of peptides.