title: Template-assisted lateral growth of amyloid-β42 fibrils studied by differential labeling with gold nanoparticles.
abstract: Amyloid-β protein (Aβ) aggregation into amyloid fibrils is central to the origin and development of Alzheimer's disease (AD), yet this highly complex process is poorly understood at the molecular level. Extensive studies have shown that Aβ fibril growth occurs through fibril elongation, whereby soluble molecules add to the fibril ends. Nevertheless, fibril morphology strongly depends on aggregation conditions. For example, at high ionic strength, Aβ fibrils laterally associate into bundles. To further study the mechanisms leading to fibril growth, we developed a single-fibril growth assay based on differential labeling of two Aβ42 variants with gold nanoparticles. We used this assay to study Aβ42 fibril growth under different conditions and observed that bundle formation is preceded by lateral interaction of soluble Aβ42 molecules with pre-existing fibrils. Based on this data, we propose template-assisted lateral fibril growth as an additional mechanism to elongation for Aβ42 fibril growth.
authors: Institute for Bioengineering of Catalonia, Baldiri Reixac 15, Barcelona, Spain.
authors: Muriel
authors: M
authors: Arimon
authors: Fausto
authors: F
authors: Sanz
authors: Ernest
authors: E
authors: Giralt
authors: Natàlia
authors: N
authors: Carulla
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D006046:Gold