Bead‐Level Characterization of Early‐Stage Amyloid β42 Aggregates: Nuclei and Ionic Concentration Effects. Issue 64 (24th October 2017)

• Record Type: Journal Article
• Authors: Hu, Dingkun; Zhao, Wei; Zhu, Yong; Ai, Hongqi; Kang, Baotao
• Is Part Of: Chemistry. Volume 23:Issue 64(2017)
• Page Start: 16257
• Page End: 16273
• Publication Date: 2017-10-24
• Subjects: aggregation -- amyloid beta peptides -- ion concentrations -- molecular modelling -- screening and covering; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201702388
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A growing body of evidence shows that soluble β‐amyloid (Aβ) aggregates, oligomers, and even protofibrils, may be more neurotoxic than fibrils. Here, we employ a coarse grain model to investigate the aggregation of 75mer Aβ42 oligomers and the salt effect, the cornerstone of fibril evolution. We find that the oligomer morphologies generated by seventy‐five monomers or mixed by both fifty monomers and five preset pentameric nuclei are different (spherical vs. bar‐/disk‐shaped) and are characterize by a full of coil content (former) and >70 % β‐turn content (latter), indicating a novel role of the nuclei played in the early aggregation stage. The aggregation for the former oligomer adopts a master‐nucleus mechanism, whereas for the latter combination of monomers and pentamers a multi‐nuclei one is found. The random salt ions will distribute around the aggregates to form several ion shells as the aggregation develops. A unique two‐fold gap between the shells is observed in the system containing 100 mm NaCl, endowing the physiological salt concentration with special implications. Meanwhile, an accurate ion–solute cutoff distance (0.66 nm) is predicted, and recommended to apply to many other aggregated biomolecular systems. The present distribution scenario of ions can be generalized to other aggregated systems, although it is strictly dependent on the identity of a specific aggregate, such as its charge and composition. Abstract : Everything changes : The nuclei and salt ions play different roles in the β‐amyloid (Aβ) aggregation process. The aggregation mechanism can change from a master‐nucleus to a multi‐nuclei mechanism, whereas the salt ions alter the composition of the secondary structure and the oligomer morphology by covering the aggregate surface with several shells formed (see figure).