Single-Particle Characterization of Aβ Oligomers in Solution

被引：104

作者：

Yusko, Erik C. ^{[1
]}

Prangkio, Panchika ^{[1
]}

Sept, David ^{[1
,2
]}

Rollings, Ryan C. ^{[3
]}

Li, Jiali ^{[3
]}

Mayer, Michael ^{[1
,4
]}

机构：

[1] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA

[3] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA

[4] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA

来源：

ACS NANO | 2012年 / 6卷 / 07期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

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; SUBMICROMETER PORES; AMYLOID FIBRILS; PEPTIDE; DISEASE; SIZE; MEMBRANE; DNA; NEUROTOXICITY; TRANSLOCATION; AGGREGATION;

D O I：

10.1021/nn300542q

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：5909 / 5919

页数：11

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