Investigating Anion Effects on Metal Ion Binding Interactions With Amyloid β Peptide by Ion Mobility Mass Spectrometry

Abstract

The study of metal ion's role in the biological processes of Alzheimer's disease has spurred investigations into the coordination chemistry of amyloid beta peptide and its fragments. Nano-electrospray ionization mass spectrometry (nESI-MS) has been utilized to examine the stabilization of bound anions on multiprotein complexes without bulk solvent. However, the effects of anions on metal ion binding interactions with amyloid beta peptide have not been explored. This study directly examined metal-peptide complexes using nESI-MS and investigated the effects of various anions on the binding ratio and stability of these complexes from ammonium salt solutions. The results indicate that different anions have distinct effects on the binding ratio and stability of various metal-peptide complexes. Of these, the bicarbonate ion exhibits the highest binding ratios for metal-peptide complexes, while binding ratios for these complexes in phosphate are comparatively low. Our results suggest that acetate, formate, bicarbonate, and phosphate have weak affinities and act as weak stabilizers of the metal-peptide complex structure in the gas phase. Intriguingly, chloride and sulfate act as stabilizers of the metal-peptide complex in the gas phase. The rank order determined from these data is substantially different from the Hofmeister salt series in solution. Although this outcome was anticipated due to the reduced influence of anions and water solvation, our findings correlate well with expected anion binding in solution and emphasize the importance of both hydration layer and anion-metal-peptide binding effects for Hofmeister-type stabilization in solution. This approach proved useful in examining the interactions between metal ions and amyloid beta peptide, which are relevant to Alzheimer's disease, using direct ESI-MS.

Keywords: amyloid‐β; anion; electrospray ionization; ion mobility; mass spectrometry.

Figure 1.

NanoESI mass spectra of 250 μM Aβ (1–10) and metal-Aβ (1–10) complex in 10mM ammonium acetate buffer.

Figure 2.

Bar graph charting binding ratio of the metal-peptide complex ion population for copper (red), zinc (green), and nickel (brown) are shown for a range of anion additives. Control data set, without added ammonium salts, are marked on the plot (Acetate).

Figure 3.

Plots of the survival yields of metal-Aβ complexes with (a) Cu ions, (b) Zn ions, (c) Ni ions in various buffer compositions are shown as a function of collision energy. Bar graphs charting collision energy required to dissociate 50% of the ion population of Aβ peptide and (d) copper, (e) zinc, (f) and nickel complexes are shown for a range of anion additives.

Figure 4.

Physical constants associated with various anions are shown through a plot of the gas-phase acidity against pKa.