Aβ₄₂ Adopts a Stronger Binding Affinity to the Gold Surface than Aβ₄₀

Area of Science:

• Biophysics
• Nanotechnology
• Neuroscience

Background:

• Soluble amyloid-beta (Aβ) oligomers, not fibrils, are key drivers of Alzheimer's disease (AD).
• The Vroman effect explains how protein binding to surfaces, like gold nanoparticles, forms a biocorona, influencing interactions.
• Gold nanoparticles offer potential for screening or removing toxic Aβ species.

Purpose of the Study:

• To investigate the binding mechanisms of Aβ40 and Aβ42 dimers to gold nanosurfaces.
• To compare the binding affinities and dissociation processes of Aβ40 and Aβ42 dimers.
• To explore the role of specific amino acid residues and structural changes in Aβ-gold interactions.

Main Methods:

• Atomistic simulations, including molecular dynamics (MD) and steered-MD (SMD).
• Analysis of binding affinity using rupture force, pulling work, and Jarzynski's free energy calculations.
• Free energy landscape analysis to study dissociation pathways.

Main Results:

• Aβ17-42 dimer shows significantly stronger binding affinity to the gold surface than Aβ17-40 dimer.
• Van der Waals (vdW) interaction energy is crucial, with Aβ17-42 exhibiting a larger vdW interaction.
• Aβ17-42 maintains a rigid β-hairpin structure during dissociation, while Aβ17-40 adopts a random coil.

Conclusions:

• The increased binding of Aβ17-42 is attributed to hydrophobic residues Ile41 and Ala42.
• Structural stability of Aβ17-42 contributes to its enhanced interaction with the gold surface.
• Understanding these differential binding properties could inform strategies for AD diagnostics and therapeutics using gold nanoparticles.