Induced β-Barrel Formation of the Alzheimer's Aβ25–35 Oligomers on Carbon Nanotube Surfaces: Implication for Amyloid Fibril Inhibition

Abstract

Recent experimental studies show that carbon nanotubes impact the aggregation process of proteins associated with neurodegenerative diseases. However, the details of molecular interactions between proteins and carbon nanotubes are still not well understood. In this study, we investigate the initial adsorption features and dynamics of the Alzheimer's amyloid-beta peptide spanning residues 25-35 (Abeta25-35) on a single-walled carbon nanotube (SWNT) surface using fully atomic molecular dynamics simulations (MD) in explicit solvent. The initial configurations of the Abeta25-35 peptides consist of two preformed bilayer beta-sheets, each with four or five beta-strands in parallel or mixed antiparallel-parallel orientations. Our simulations show, for what we believe is the first time, that two disjointed Abeta25-35 beta-sheets with mixed antiparallel-parallel strands can assemble into beta-barrels wrapping the SWNT. In contrast, both simulations of Abeta25-35 without SWNT, and simulations of SWNT-Abeta25-35 with purely parallel beta-strands, lead to disordered aggregates. We find that Abeta25-35 beta-barrel formation involves at least two steps: i), curving of the Abeta25-35 beta-sheets as a result of strong hydrophobic interactions with carbon nanotube concomitantly with dehydration of the SWNT-peptide interface; and ii), intersheet backbone hydrogen bond formation with fluctuating intrasheet hydrogen bonds. Detailed analysis of the conversion shows that beta-barrel formation on SWNT surface results from the interplay of dehydration and peptide-SWNT/peptide-peptide interactions. Implications of our results on amyloid fibril inhibition are discussed.

Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer Disease

“…Constraining the b-turn by linking Asp23 to Lys28 also results in a system with increased fibrillogenic propensity (Reddy et al 2009a). Placing the b-turn on a constraining physical interface also affects assembly (Fu et al 2009), and this could have implications for Ab assembly when some of the peptide is bound to cell membranes, as is likely in the brain. Assembly at low or neutral pH may have an effect on the registration of the subunits within the fibril (Negureanu and Baumketner 2009).…”

Chiral Metallohelical Complexes Enantioselectively Target Amyloid β for Treating Alzheimer’s Disease

“…Previous studies have shown that Aβ25-35 fragment similar with Aβ1-40 can form Aβ fibrils [43][44][45] . However, under our experimental conditions, both the inhibition and destabilization effects of these metal complexes on Aβ25-35 exhibited much weaker ( Figure S8B, S12 and Table 1).…”

Influence of Au nanoparticles on the aggregation of amyloid-β-(25–35) peptides

“…The utilization of nanoparticles for the treatment of proteinaggregation diseases is an important one among these applications. [23][24][25][26] But researches on the interaction between Au NPs and Ab proteins have not been reported yet, due to the computationally huge simulations required to simulate all the NP atoms, especially for large NPs. [10][11][12][13][14][15][16][17][18][19][20][21][22] By now, the phenomena of the inuence of Au NPs on the Ab protein aggregations has already been reported using various techniques such as scanning electron microscopy, transmission electron microscopy, atom force microscopy and optical spectroscopies.…”