Visualization and classification of amyloid β supramolecular assemblies
Visualization and classification of amyloid β supramolecular assemblies
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DOI：
10.1021/bi701842n
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发表时间：
2007-12-25
期刊：
影响因子：
2.9
通讯作者：
Goto, Yuji
中科院分区：
文献类型：
--
作者：
Yagi, Hisashi;Ban, Tadato;Goto, Yuji
淀粉样蛋白β（A β）原纤维的沉积已被认为在阿尔茨海默病中起核心作用。在阐明纤维形成的机制以及开发淀粉样变性的新治疗方法方面，直接观察是重要的。专注于在早期阶段与表面的相互作用，我们研究了石英片上A β（1-40）原纤维的自发形成，通过全内反射荧光显微镜结合硫磺素T（一种淀粉样蛋白特异性荧光染料）进行监测。A β（1-40）的自组装，由低浓度的十二烷基硫酸钠加速，产生各种显着的淀粉样蛋白组装体。典型地观察到具有径向原纤维生长的致密堆积的球晶结构。当原纤堆积较粗时，球晶核中往往会伸出极长的原纤。在其他情况下，形成了大量的蠕虫状原纤维。透射电子显微镜和原子力显微镜发现相对较短和直的纤维块相关的横向没有紧密的相互作用，导致随机行走样原纤维生长。这些结果表明，在自发性纤维化过程中，与表面接触时发生的成核很容易受到环境因素的影响，产生各种类型的核，从而产生淀粉样蛋白形态的变化。淀粉样蛋白超分子组装体的分类将有助于阐明淀粉样蛋白纤维的结构-功能关系。
Deposition of amyloid beta (A beta) fibrils has been suggested to play a central role in Alzheimer's disease. In clarifying the mechanism by which fibrils form and moreover in developing new treatments for amyloidosis, direct observation is important. Focusing on the interactions with surfaces at the early stages, we studied the spontaneous formation of A beta(1-40) fibrils on quartz slices, monitored by total internal reflection fluorescence microscopy combined with thioflavin T, an amyloid-specific fluorescence dye. Self-assembly of A beta(1-40), accelerated by a low concentration of sodium dodecyl sulfate, produced various remarkable amyloid assemblies. Densely packed spherulitic structures with radial fibril growth were typically observed. When the packing of fibrils was coarse, extremely long fibrils often protruded from the spherulitic cores. In other cases, a large number of wormlike fibrils were formed. Transmission electron microscopy and atomic force microscopy revealed relatively short and straight fibrillar blocks associated laterally without tight interaction, leading to random-walk-like fibril growth. These results suggest that, during spontaneous fibrillation, the nucleation occurring in contact with surfaces is easily affected by environmental factors, creating various types of nuclei, and hence variations in amyloid morphology. A taxonomy of amyloid supramolecular assemblies will be useful in clarifying the structure-function relationship of amyloid fibrils.