Figure 1.
A schematic of experimental setup of force spectroscopy experiment showing Aβ bound to substrate and tip via the PEG linker.
Figure 2.
Effect of Copper on Aβ rupture force.
Histograms show the distribution of forces required to rupture the Aβ-Aβ complex without copper (A) and with copper (B). Fits to the data are Gaussian distributions, the peaks of which represent the most probable rupture force.
Table 1.
Statistical Data of Force Spectroscopy Experiments.
Figure 3.
Force curves showing rupture forces of an Aβ dimer without (A) and with (B) copper added at a retraction rate of 400 nm/s. Curves are shown as force vs. piezo z-displacement.
Figure 4.
AFM images of amyloid-metal aggregates.
AFM images of Aβ incubated without copper for periods of 1 hr (A) 6 hr (B) and 24 hr (C), and with copper at a 10∶1 molar ratio for 1 hr (D), 6 hr (E), and 24 hr (F). The lateral scale bar is 1 µm.
Figure 5.
Schematic diagram of Aβ dimers with and without copper.
Without copper, the most favorable conformation of the Aβ dimer involves an anti-parallel conformation (A). With the addition of copper, Aβ adopts a parallel dimer conformation (B) stabilized by the occupied copper binding sites (C).
Figure 6.
Proposed structures of Aβ dimers with and without copper assembled from stable Aβ(1–42) monomer structures.
Each monomer has an internal antiparallel β-sheet between residues 18–21 and 30–33. The dimers are assembled by juxtaposition of the self-recognition site residues 18–21 in antiparallel (A, C) and parallel (B, D) orientation. Both orientations bring His6, His13 and His14 of each monomer into close proximity, requiring little reorientation to bind Cu2+ ions (filled green circles). Structures are courtesy of D. F. Raffa and A. Rauk, Molecular Dynamics Study of the Beta Amyloid Peptide of Alzheimer's Disease and its Divalent Copper Complexes [53], created using Raswin software.