Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Nano. 2012 Jul 24;6(7):5909-19. doi: 10.1021/nn300542q. Epub 2012 Jun 21.
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.
确定淀粉样蛋白在淀粉样相关疾病中的病理作用,需要一种方法来高分辨率地描述淀粉样寡聚体在大小和形状上的动态分布。在这里,我们探索了通过脂质双层覆盖的纳米孔进行电阻脉冲感应的潜力,以直接在溶液中且无需化学修饰的情况下测量单个淀粉样β寡聚体的大小。该方法将单个淀粉样β聚集物分类为球形寡聚体、原纤维或成熟纤维,并能够解释淀粉样β聚集物大小的巨大异质性。该方法揭示了原纤维长度(12 至 155 聚体)以及原纤维和纤维的平均横截面积的分布。