Graduate School of Engineering Science , Osaka University , Toyonaka , Osaka 560-8531 , Japan.
Graduate School of Engineering , Osaka University , Suita , Osaka 565-0871 , Japan.
Langmuir. 2018 May 15;34(19):5474-5479. doi: 10.1021/acs.langmuir.8b00639. Epub 2018 May 8.
Unlike previous in vitro measurements where Amyloid β (Aβ) aggregation was studied in bulk solutions, we detect the structure change of the Aβ aggregate on the surface of a wireless quartz-crystal-microbalance biosensor, which resembles more closely the aggregation process on the cell membrane. Using a 58 MHz quartz crystal, we monitored changes in the viscoelastic properties of the aggregate formed on the quartz surface from monomers to oligomers and then to fibrils, involving up to the 7th overtone mode (406 MHz). With atomic-force microscopy observations, we found a significant stiffness increase as well as thinning of the protein layer during the structure change from oligomer to fibrils at 20 h, which indicates that the stiffness of the fibril is much higher. Viscoelasticity can provide a significant index of fibrillation and can be useful for evaluating inhibitory medicines in drug development.
与以往在大量溶液中研究淀粉样蛋白 β（Aβ）聚集的体外测量不同，我们在无线石英晶体微天平生物传感器的表面上检测到 Aβ 聚集体的结构变化，这更接近细胞膜上的聚集过程。我们使用 58 MHz 的石英晶体监测了从单体到低聚物再到原纤维形成的聚集体在石英表面上的粘弹性特性的变化，涉及到第 7 次泛音模式（406 MHz）。通过原子力显微镜观察，我们发现，在 20 小时内，从低聚物到原纤维的结构变化过程中，蛋白质层的显著硬度增加和变薄，这表明原纤维的硬度要高得多。粘弹性可以为纤维形成提供一个重要的指标，并可用于评估药物开发中的抑制药物。
