Abstract
Amyloids-β (Aβ) fibrils are involved in several neurodegenerative diseases. In this study, atomistic molecular dynamics simulations have been used to investigate how monolayer-protected gold nanoparticles interact with Aβ(1-40) and Aβ(1-42) fibrils. Our results show that small gold nanoparticles bind with the external side of amyloid-β fibrils that is involved in the fibrillation process. The binding affinity, studied for both kinds of fibrils as a function of the monolayer composition and the nanoparticle diameter, is modulated by hydrophobic interactions and ligand monolayer conformation. Our findings thus show that monolayer-protected nanoparticles are good candidates to prevent fibril aggregation and secondary nucleation or to deliver drugs to specific fibril regions.
Highlights
Amyloid fibrils constitute a group of proteins involved in neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) disease.[1,2] In particular, β-amyloid peptides (Aβ1−40 and Aβ1−42) are responsible for fibrous plaque formation in AD,[3] which causes a progressive loss of memory, cognitive deprivation, and death to patients.[4]
Shape monomer which is stabilized by a salt bridge between residue D23 and residue K28, which correspond to aspartic acid and lysine, respectively.[7−9] The protofibril is made by parallel β-strands where the two β-sheets, called β-1 and β-2, are perpendicular to the fibril axis, and adjacent monomers are stabilized by hydrogen bonds.[7]
To elucidate the interaction of monolayer-coated AuNPs with both Aβ(1−42) and Aβ(1−40) fibrils, we simulated monolayer-coated AuNPs with a core diameter of 2 and 5 nm interacting with a nonmature protofibril, by means of atomistic molecular dynamics (MD) simulations
Summary
Amyloid fibrils constitute a group of proteins involved in neurodegenerative (typically fatal) diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) disease.[1,2] In particular, β-amyloid peptides (Aβ1−40 and Aβ1−42) are responsible for fibrous plaque formation in AD,[3] which causes a progressive loss of memory, cognitive deprivation, and death to patients.[4]. Amyloid-β fibrils are made by two β-sheets forming a U-. Shape monomer which is stabilized by a salt bridge between residue D23 and residue K28, which correspond to aspartic acid and lysine, respectively.[7−9] The protofibril is made by parallel β-strands where the two β-sheets, called β-1 and β-2, are perpendicular to the fibril axis, and adjacent monomers are stabilized by hydrogen bonds.[7] It is recognized that amyloid-β fibrils grow in two distinct ways.[1,10] The addition of A-β monomers to the ends of the fibril along the fibril axis produces fibril elongation, whereas the lateral binding of two fibrils along the fibril axis brings about the formation of the protofilament.[11]
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