Nanoelectrical characterization of amyloid-β ₄₂ aggregates via Kelvin probe force microscopy

Biological processes related to amyloid-β (Aβ) aggregation and deposition are associated with the onset of Alzheimer’s disease. Although these processes are attributed to electrostatic interactions between the Aβ₄₂ sequences, the electrical properties of Aβ aggregates (i.e., oligomers and fibrils) have not yet been fully explored despite their importance. Here, we investigated the nanoelectrical properties (i.e., surface potential) of Aβ₄₂ aggregates using Kelvin probe force microscopy (KPFM) and found that the surface potential of the Aβ₄₂ aggregates was changed from positive to negative with pH, passing across zero surface potential at pH=5.2-5.4. The measured surface potentials were ranged from 48 to -35 mV/nm for both the oligomers and the fibrils. From our observations, we determined the isoelectric points (pIs) of both cases. Using the commercial software PyMOL, we also converted the surface potential of a single monomorphic Aβ₄₂ fibril; in the simulation, we calculated the net charges of the monomorphic fibrils depending on pH, predicted its pI by Boltzmann curve fitting, and compared these results with our experimental KPFM data.