Engineering amyloid fibrils from β-solenoid proteins for biomaterials applications.

Engineering amyloid fibrils from β-solenoid proteins for biomaterials applications.
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从 β-螺线管蛋白中工程化淀粉样原纤维,用于生物材料应用。

DOI:
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发表时间:
2015
期刊:
影响因子:
17.1
通讯作者:
D. Cox
D. Cox
中科院分区:
材料科学1区
文献类型:
--
作者:
Maria D R Peralta;Á. Karsai;A. Ngo;Catherine Sierra;Kai T. Fong;N. R. Hayre;Nima Mirzaee;Krishnakumar M. Ravikumar;Alexander Kluber;Xi Chen;Gang;M. Toney;Rajiv Singh;D. Cox

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自然界提供了许多自组装的例子,这些例子可以潜在地用于材料应用。一维交叉β或淀粉样蛋白结构已受到相当大的关注,其可用作线生长或强化材料(如胶水或水泥)的模板。在这里,我们展示了基于β螺线管蛋白修饰的受控淀粉样蛋白自组装。它们在几种情况下自然发生(例如,抗冻蛋白、耐药蛋白),但由于其末端的加帽结构或扭曲而不在体内聚集。去除这些加帽结构和云杉芽虫和黑麦草抗冻蛋白末端的规则化产生具有可预测高度的微米长度的淀粉样蛋白原纤维,其可以是基于生物材料的自组装的平台。设计过程中,包括全原子分子动力学模拟,纯化和自组装程序进行了说明。原纤维形成的预测特性的支持证据,从硫磺素-T荧光,圆二色性,动态光散射,原子力显微镜。此外,我们发现证据的修改云杉芽虫抗冻原纤维与足够的孵育时间的侧向组装。聚合的动力学与其他淀粉样蛋白形成反应的动力学一致,并且由于聚合核的预形成性质而相对较快。
Nature provides numerous examples of self-assembly that can potentially be implemented for materials applications. Considerable attention has been given to one-dimensional cross-β or amyloid structures that can serve as templates for wire growth or strengthen materials such as glue or cement. Here, we demonstrate controlled amyloid self-assembly based on modifications of β-solenoid proteins. They occur naturally in several contexts (e.g., antifreeze proteins, drug resistance proteins) but do not aggregate in vivo due to capping structures or distortions at their ends. Removal of these capping structures and regularization of the ends of the spruce budworm and rye grass antifreeze proteins yield micron length amyloid fibrils with predictable heights, which can be a platform for biomaterial-based self-assembly. The design process, including all-atom molecular dynamics simulations, purification, and self-assembly procedures are described. Fibril formation with the predicted characteristics is supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy. Additionally, we find evidence for lateral assembly of the modified spruce budworm antifreeze fibrils with sufficient incubation time. The kinetics of polymerization are consistent with those for other amyloid formation reactions and are relatively fast due to the preformed nature of the polymerization nucleus.
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