对β-粉样纤维生长的多态特异性动力学和热力学
Wei Qiang1, Kevin Kelley, Robert Tycko
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States.
Journal of the American Chemical Society
|May 1, 2013
概括
两个粉样β (Aβ(1-40)) 纤维的多态表现出不同的生长动力学和稳定性. 动的 (A) 多态更稳定,碎片不同,解释了其在动溶液中的普遍性.
科学领域:
- 生物化学 生物化学
- 生物物理学的生物物理.
- 材料科学 材料科学 材料科学
背景情况:
- 粉样蛋白纤维,特别是来自粉样蛋白β (Aβ(1-40) 的纤维,以其结构多态性而闻名.
- 不同Aβ(1-40) 纤维分子多态的物理性质和热力学稳定性尚未完全理解.
- 从固态核磁共振 (NMR) 研究中可获得两个不同的Aβ(1-40) 多态的结构模型.
研究的目的:
- 为了研究和比较两个特定的Aβ(1-40) 纤维分子多态的生长动力学和热力学稳定性.
- 阐明这些多态的结构差异和功能性质之间的关系.
- 了解在不同条件下影响某些多态体占主导地位的因素.
主要方法:
- 用原子力显微镜 (AFM) 测量了种子纤维的延长和收缩率.
- 在准平衡状态下,可溶性Aβ(1-40) 度由动力速率确定,并通过紫外线吸收度测量证实.
- 固态核磁共振被用来监测在24°C的多态体之间的相互转换.
- 在剪切力下评估了碎片化速率.
主要成果:
- 在24°C时,这两种多态体表现出不同的延长/收缩动力学,但具有相似的热力学稳定性;激动的 (A) 多态体比静止的 (Q) 多态体更稳定.
- 在37°C时,动力差异减少,热力学稳定性在两种多态体中显著增加.
- AFM数据支持间歇性纤维细胞生长模型.
- 在剪切应力下,A多态碎片化速度与Q多态碎片化速度明显不同.
结论:
- 动力学和热力学特性在Aβ(1-40) 纤维分子多态体之间有显著的差异,受温度的影响.
- 兴奋 (A) 多态的更大的稳定性和明显的碎片化行为,有助于其在兴奋生长条件下的流行.
- 了解多态特异性属性对于破译粉样纤维的形成及其影响至关重要.
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