Journal
ACS NANO
Volume 6, Issue 7, Pages 5909-5919Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn300542q
Keywords
nanopore; single molecule; bilayer-coated nanopore; amyloid-beta oligomer; amyloid aggregate; amyloid fiber; protofibril; resistive pulse; cluster analysis; Coulter counter; size distribution; bootstrap resampling; cumulative distribution function; probability density function
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Funding
- National Science Foundation [0449088, 0315633]
- National Institutes of Health [1R01GM081705]
- National Human Genome Research Institute [HG003290, HG004776]
- government of Thailand
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0449088] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [0315633] Funding Source: National Science Foundation
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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-beta oligomers directly in solution and without chemical modification. This method classified individual amyloid-beta aggregates as spherical oligomers, protofibrils, or mature fibers and made it possible to account for the large heterogeneity of amyloid-P 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.
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