Taylor Dispersion Analysis and Atomic Force Microscopy Provide a Quantitative Insight into the Aggregation Kinetics of Aβ (1–40)/Aβ (1–42) Amyloid Peptide Mixtures

Mihai Deleanu (1) , Olivier Deschaume (2) , Luca Cipelletti (3) , Jean-François Hernandez (1) , Carmen Bartic (2) , Hervé Cottet (1) , Joseph Chamieh (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
3 L2C - Laboratoire Charles Coulomb

Aggregation of amyloid β peptides is known to be one of the main processes responsible for Alzheimer's disease. The resulting dementia is believed to be due in part to the formation of potentially toxic oligomers. However, the study of such intermediates and the understanding of how they form is very challenging because they are heterogeneous and transient in nature. Unfortunately, few techniques can quantify, in real time, the proportion and the size of the different soluble species during the aggregation process. In a previous work (Deleanu et al. Anal. Chem. 2021), we showed the potential of Taylor dispersion analysis (TDA) in amyloid speciation during the aggregation process of Aβ(1-40) and Aβ(1-42). The current work aims at exploring in detail the aggregation of amyloid Aβ(1-40):Aβ(1-42) peptide mixtures with different proportions of each peptide (1:0, 3:1, 1:1, 1:3 and 0:1), using TDA and atomic force microscopy (AFM). TDA allowed for monitoring the kinetics of the amyloid assembly and quantifying the transient intermediates. Complementarily, AFM allowed the formation of insoluble fibrils to be visualized. Together, the two techniques enabled to study the influence of the peptide ratios on the kinetics and the formation of potentially toxic oligomeric species.

Mots clés: Taylor dispersion analysis; AFM; peptide aggregation; oligomers; amyloid beta peptides; diffusion coefficient; hydrodynamic radius; Taylor dispersion analysis

Domaines: Neurobiologie

Mihai Deleanu, Olivier Deschaume, Luca Cipelletti, Jean-François Hernandez, Carmen Bartic, et al.. Taylor Dispersion Analysis and Atomic Force Microscopy Provide a Quantitative Insight into the Aggregation Kinetics of Aβ (1–40)/Aβ (1–42) Amyloid Peptide Mixtures. ACS Chemical Neuroscience, 2022, 13 (6), pp.786-795. ⟨10.1021/acschemneuro.1c00784⟩. ⟨hal-03801189⟩