The opposite effects of Cu(II) and Fe(III) on the assembly of glucagon amyloid fibrils

A few transition metal ions are strongly implicated as co-factors in modulating the aggregation of amyloid peptides, which is believed to be a key factor in regulating the cytotoxicity of peptides. In this paper, we explored the effects of Cu(II) and Fe(III) on the aggregation/fibrillation of glucagon peptides using various biophysical techniques. AFM analysis demonstrated that Cu(II) could promote the conversion of glucagon peptides into amyloid fibrils, while the formation of fibrils was profoundly suppressed in the presence of Fe(III). Strikingly, at higher Cu(II) concentration (200 mu M), spherical assemblies were predominant with abundant fibrils protruding from spherical cores. However, only globular aggregates of several nanometers size were observed when the concentration of Fe(III) was increased beyond 100 mu M. In addition, it was also found that the FTIR and CD spectra of glucagon co-incubated with Cu(II) or Fe(III) remarkably differed from that in the absence of ions. These results strongly suggested that Cu(II) and Fe(III) could dramatically modify the morphologies as well as the secondary structures of aggregates during the spontaneous fibrillation of glucagon. Our study could shed light on how the metal ions regulate the amyloid aggregation of glucagon peptide, and might provide a controllable means for the synthesis of amyloid nanostructures for future technological applications.