The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush

The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush
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病理性人类 Tau 原纤维的毛茸茸的外套是两层聚电解质刷

DOI:
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发表时间:
2012
影响因子:
11.1
通讯作者:
D. Müller
D. Müller
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Susanne Wegmann;Izhar D Medalsy;E. Mandelkow;D. Müller

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在神经退行性疾病中积累的淀粉样蛋白样Tau原纤维的结构和性质已经争论了几十年。尽管Tau原纤维的核心是由短的β-链组装而成,但从原纤维核心突出的更长的非结构化Tau结构域的性质在很大程度上仍然不清楚。利用免疫金透射电镜和力-体积原子力显微镜(AFM),我们对人类Tau原纤维进行了高分辨率成像,并同时绘制了它们的力学和粘附特性。Tau原纤维由非结构化的短c端和长n端Tau结构域组成,具有约16纳米厚的绒毛外衣,类似于两层聚电解质电刷。模糊涂层的机械和粘合性能受电解质和pH值的调节,因此受细胞环境的调节。绒毛被的这些独特特性有助于理解Tau原纤维如何干扰细胞相互作用并在神经原纤维缠结中积累。
The structure and properties of amyloid-like Tau fibrils accumulating in neurodegenerative diseases have been debated for decades. Although the core of Tau fibrils assembles from short β-strands, the properties of the much longer unstructured Tau domains protruding from the fibril core remain largely obscure. Applying immunogold transmission EM, and force-volume atomic force microscopy (AFM), we imaged human Tau fibrils at high resolution and simultaneously mapped their mechanical and adhesive properties. Tau fibrils showed a ≈16-nm–thick fuzzy coat that resembles a two-layered polyelectrolyte brush, which is formed by the unstructured short C-terminal and long N-terminal Tau domains. The mechanical and adhesive properties of the fuzzy coat are modulated by electrolytes and pH, and thus by the cellular environment. These unique properties of the fuzzy coat help in understanding how Tau fibrils disturb cellular interactions and accumulate in neurofibrillary tangles.
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