A novel form of β-strand assembly observed in Aβ_33–42adsorbed onto graphene

Abstract

Peptide assembly plays a seminal role in the fabrication of structural and functional architectures in cells. Characteristically, peptide assemblies are often dominated by β-sheet structures, wherein component molecules are connected by backbone hydrogen bonds in a parallel or an antiparallel fashion. While β-rich peptide scaffolds are implicated in an array of neurodegenerative diseases, the mechanisms by which toxic peptides assemble and mediate neuropathic effects are still poorly understood. In this work, we employ molecular dynamics simulations to study the adsorption and assembly of the fragment Aβ33-42 (taken from the Aβ-42 peptide widely associated with Alzheimer's disease) on a graphene surface. We observe that such Aβ33-42 fragments, which are largely hydrophobic in character, readily adsorb onto the graphitic surface and coalesce into a well-structured, β-strand-like assembly. Strikingly, the structure of such complex is quite unique: hydrophobic side-chains extend over the graphene surface and interact with adjacent peptides, yielding a well-defined mosaic of hydrophobic interaction patches. This ordered structure is markedly depleted of backbone hydrogen bonds. Hence, our simulation results reveal a distinct type of β-strand assembly, maintained by hydrophobic side-chain interactions. Our finding suggests the backbone hydrogen bond is no longer crucial to the peptide assembly. Further studies concerning whether such β-strand assembly can be realized in other peptide systems and in biologically-relevant contexts are certainly warranted.

Self-assembly of the full-length amyloid Aβ42 protein in dimers

“…The hydrophobic interaction, rather than backbone hydrogen bonding, is crucial for the Aβ42 interaction, consistent with recent evidence. 50 Qualitatively, these findings are in agreement with the characterization of early-stage Aβ42 aggregates by CD and ThT fluorescence that show that the oligomers have a low β-content. 17,51 …”

Surface Inhomogeneity of Graphene Oxide Influences Dissociation of Aβ16–21 Peptide Assembly

“…Accumulating evidence has shown that Aβ peptides can adsorb onto the cell membrane , and other material surfaces − and that their self-assembly can be significantly influenced by these substrate surfaces. A better understanding of the interaction between Aβ and those surfaces thus might provide new insights to the underlying mechanism of the peptide assembly as well as the development of potential therapeutic strategies against AD.…”

Length-Dependent Structural Transformations of Huntingtin PolyQ Domain Upon Binding to 2D-Nanomaterials

“…Both graphene and MoS 2 nanosheets have a highly hydrophobic surface with large water contact angles (despite that MoS 2 has partial charges on Mo and S atoms), offering a biomimetic environment for protein binding when interfaced with water (Mathesh et al, 2016;Gu et al, 2017;Zhang et al, 2017). Previous studies have observed a variety of effects of graphene on proteins, including disruption of protein structures (Zuo et al, 2011;Chong et al, 2015;Wang et al, 2015), enhancement of enzymatic activity (Mathesh et al, 2016), and potential interference of protein-protein interactions (Luan et al, 2015(Luan et al, , 2016aFeng et al, 2016). Comparatively, there are less studies on MoS 2 's effect on proteins partly due to the lack of appropriate potential function parameters for MoS 2 simulation.…”