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
收藏
页码：5909 / 5919
页数：11
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