Single-particle characterization of Aβ oligomers in solution.
Determining the pathological role of amyloids in amyloid-associated diseases will require a method for characterizing the dynamic distributions in size and shape of amyloid oligomers with high resolution. Here, we explored the potential of resistive-pulse sensing through lipid bilayer-coated nanopores to measure the size of individual amyloid-β oligomers directly in solution and without chemical modification. This method classified individual amyloid-β aggregates as spherical oligomers, protofibrils, or mature fibers and made it possible to account for the large heterogeneity of amyloid-β aggregate sizes. The approach revealed the distribution of protofibrillar lengths (12- to 155 -mer) as well as the average cross-sectional area of protofibrils and fibers.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
Erik C
EC
Yusko
Panchika
P
Prangkio
David
D
Sept
Ryan C
RC
Rollings
Jiali
J
Li
Michael
M
Mayer
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry; D046210:Microfluidic Analytical Techniques; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D058608:Nanopores / Q000648:ultrastructure; D036103:Nanotechnology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000648:ultrastructure; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012996:Solutions
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D012996:Solutions; C078592:amyloid beta-protein (1-40)