Influence of the β-Sheet Content on the Mechanical Properties of Aggregates during Amyloid Fibrillization
Influence of the β-Sheet Content on the Mechanical Properties of Aggregates during Amyloid Fibrillization
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DOI：
10.1002/anie.201409050
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发表时间：
2015-02-16
影响因子：
16.6
通讯作者：
Dietler, Giovanni
中科院分区：
文献类型：
--
作者：
Ruggeri, Francesco Simone;Adamcik, Jozef;Dietler, Giovanni
与神经退行性疾病相关的淀粉样纤维，如帕金森氏症和阿尔茨海默氏症，由不可溶的突触核蛋白和A-42蛋白聚集体组成，片状含量较高。这两种蛋白质的聚集是通过单体的错误折叠发生的，并通过形成中间低聚物和原纤维物种来进行，从而形成最终的纤维交叉片状结构。用硫代黄素T荧光和圆二色谱结合AFM峰力定量纳米力学技术研究了胶凝过程中形成的齐聚物、原纤维和原纤维的形态和力学性能。结果表明，在低聚物向成熟纤维转变的过程中，其杨氏模数有所增加，从而推测其力学性能的差异是由于内部结构从无规卷曲转变为片层含量增加的结构所致。
Amyloid fibrils associated with neurodegenerative diseases, such as Parkinson's and Alzheimer's, consist of insoluble aggregates of -synuclein and A-42 proteins with a high -sheet content. The aggregation of both proteins occurs by misfolding of the monomers and proceeds through the formation of intermediate oligomeric and protofibrillar species to give the final fibrillar cross--sheet structure. The morphological and mechanical properties of oligomers, protofibrils, and fibrils formed during the fibrillization process were investigated by thioflavinT fluorescence and circular dichroism in combination with AFM peak force quantitative nanomechanical technique. The results reveal an increase in the Young's modulus during the transformation from oligomers to mature fibrils, thus inferring that the difference in their mechanical properties is due to an internal structural change from a random coil to a structure with increased -sheet content.