Amyloid fibrils nucleated and organized by DNA origami constructions.

Amyloid fibrils nucleated and organized by DNA origami constructions.
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DOI:
10.1038/nnano.2014.102
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发表时间:
2014-07
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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淀粉样原纤维是有序的不溶性蛋白质聚集体,与神经退行性疾病如阿尔茨海默病相关。原纤维具有共同的棒状芯结构,由细长的β-链堆叠形成,并且具有类似于丝的刚性(杨氏模量为0.2-14 Gpa)。它们还表现出高的热稳定性和化学稳定性,并且可以在体外由短的合成非疾病相关肽组装。因此,它们在开发用于生物纳米技术应用的自组装材料方面具有重大意义。合成DNA分子以前曾被用于形成复杂的结构和组织其他材料,如金属纳米颗粒,原则上可以用于成核和组织淀粉样蛋白原纤维。在这里,我们表明,DNA折纸纳米管可以鞘内形成的淀粉样纤维。通过修饰对应于淀粉样蛋白转甲状腺素蛋白(TTR)的残基105-115的合成肽片段来构建原纤维,并且使用DNA折纸构建体来形成20-螺旋DNA纳米管,其中具有足够的空间用于内部的原纤维。一旦形成,纤维填充的纳米管可以通过DNA-DNA杂交相互作用组织到预定义的二维平台上。
Amyloid fibrils are ordered, insoluble protein aggregates that are associated with neurodegenerative conditions such as Alzheimer’s disease. The fibrils have a common rod-like core structure, formed from an elongated stack of β-strands, and have a rigidity similar to silk (Young’s modulus of 0.2-14 Gpa). They also exhibit high thermal and chemical stability, and can be assembled in vitro from short synthetic non-disease-related peptides. As a result, they are of significant interest in the development of self-assembled materials for bionanotechnology applications. Synthetic DNA molecules have previously been used to form intricate structures and organize other materials such as metal nanoparticles, and could in principle be used to nucleate and organize amyloid fibrils. Here we show that DNA origami nanotubes can sheathe amyloid fibrils formed within them. The fibrils are built by modifying the synthetic peptide fragment corresponding to residues 105-115 of the amyloidogenic protein transthyretin (TTR), and a DNA origami construct is used to form 20-helix DNA nanotubes with sufficient space for the fibrils inside. Once formed, the fibril-filled nanotubes can be organized onto predefined two-dimensional platforms via DNA-DNA hybridization interactions.
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