Laboratory of Physics of Living Matter, Ecole Polytechnique Fédérale de Lausanne (EPFL), Route de la Sorge, 1015 Lausanne (Switzerland).
Angew Chem Int Ed Engl. 2015 Feb 16;54(8):2462-6. doi: 10.1002/anie.201409050. Epub 2015 Jan 14.
Amyloid fibrils associated with neurodegenerative diseases, such as Parkinson's and Alzheimer's, consist of insoluble aggregates of α-synuclein and Aβ-42 proteins with a high β-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-β-sheet structure. The morphological and mechanical properties of oligomers, protofibrils, and fibrils formed during the fibrillization process were investigated by thioflavin T 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 β-sheet content.
与神经退行性疾病（如帕金森病和阿尔茨海默病）相关的淀粉样纤维由不溶性聚集的α-突触核蛋白和 Aβ-42 蛋白组成，具有高 β-折叠含量。两种蛋白质的聚集通过单体的错误折叠发生，并通过形成中间寡聚体和原纤维物种进行，从而产生最终的纤维状交叉 β-折叠结构。通过硫黄素 T 荧光和圆二色性与 AFM 峰值力定量纳米力学技术相结合，研究了纤维形成过程中形成的寡聚物、原纤维和纤维的形态和力学性质。结果表明，在从寡聚物到成熟纤维的转化过程中杨氏模量增加，因此推断它们的力学性质差异是由于内部结构从无规卷曲到增加β-折叠含量的结构的变化。
