Mechanical manipulation of Alzheimer's amyloid β1-42 fibrils
Mechanical manipulation of Alzheimer's amyloid β1-42 fibrils
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DOI：
10.1016/j.jsb.2005.12.015
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发表时间：
2006-08-01
影响因子：
3
通讯作者：
Kellermayer, M. S. Z.
中科院分区：
文献类型：
--
作者：
Karsai, A.;Martonfalvi, Zs.;Kellermayer, M. S. Z.
39至42个残基长的淀粉样β肽（A β肽）在阿尔茨海默病患者的神经纤维中发现的神经炎斑块中形成丝状结构。A β-原纤维的组装和沉积是这种神经退行性疾病发病机制中最重要的因素之一。虽然淀粉样蛋白原纤维的结构分析是困难的，单分子方法可以提供独特的见解，他们的特点。在目前的工作中，我们探讨了纳米力学性质的淀粉样蛋白原纤维形成的全长，最神经毒性的A β 1 - 42肽，通过操纵单个原纤维与原子力显微镜。我们表明，A β-亚基片可以从原纤维表面机械解压缩与恒定的力在可逆的过渡。基本解链力（类似于23 pN）显著低于先前对于由A β 1 - 40肽形成的原纤维所观察到的解链力（类似于33 pN），表明在肽的C-末端存在两个额外残基（Ile和Ala）导致原纤维的机械不稳定。偏离恒定力转变可能是由于其左手螺旋结构引起的原纤维内的几何约束的结果。A β 1 - 42的纳米机械指纹进一步受到原纤维内相互作用的结构动力学的影响。(c)2006年爱思唯尔公司All rights reserved.
The 39- to 42-residue-long amyloid beta-peptide (A beta-peptide) forms filamentous structures in the neuritic plaques found in the neuropil of Alzheimer's disease patients. The assembly and deposition of A beta-fibrils is one of the most important factors in the pathogenesis of this neurodegenerative disease. Although the structural analysis of amyloid fibrils is difficult, single-molecule methods may provide unique insights into their characteristics. In the present work, we explored the nanomechanical properties of amyloid fibrils formed from the full-length, most neurotoxic A beta 1-42 peptide, by manipulating individual fibrils with an atomic force microscope. We show that A beta-subunit sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition. The fundamental unzipping force (similar to 23 pN) was significantly lower than that observed earlier for fibrils formed from the A beta 1-40 peptide (similar to 33 pN), suggesting that the presence of the two extra residues (Ile and Ala) at the peptide's C-terminus result in a mechanical destabilization of the fibril. Deviations from the constant force transition may arise as a result of geometrical constraints within the fibril caused by its left-handed helical structure. The nanomechanical fingerprint of the A beta 1-42 is further influenced by the structural dynamics of intrafibrillar interactions. (c) 2006 Elsevier Inc. All rights reserved.