Hanke Marcel, Gonzalez Orive Alejandro, Grundmeier Guido, Keller Adrian
Technical and Macromolecular Chemistry, Paderborn University, Warburger Str. 100, 33098 Paderborn, Germany.
Department of Chemistry, University of La Laguna, P.O. Box 456, E-38200 La Laguna, Spain.
Nanomaterials (Basel). 2020 Nov 4;10(11):2200. doi: 10.3390/nano10112200.
The aggregation of human islet amyloid polypeptide (hIAPP) plays a major role in the pathogenesis of type 2 diabetes mellitus (T2DM), and numerous strategies for controlling hIAPP aggregation have been investigated so far. In particular, several organic and inorganic nanoparticles (NPs) have shown the potential to influence the aggregation of hIAPP and other amyloidogenic proteins and peptides. In addition to conventional NPs, DNA nanostructures are receiving more and more attention from the biomedical field. Therefore, in this work, we investigated the effects of two different DNA origami nanostructures on hIAPP aggregation. To this end, we employed in situ turbidity measurements and ex situ atomic force microscopy (AFM). The turbidity measurements revealed a retarding effect of the DNA nanostructures on hIAPP aggregation, while the AFM results showed the co-aggregation of hIAPP with the DNA origami nanostructures into hybrid peptide-DNA aggregates. We assume that this was caused by strong electrostatic interactions between the negatively charged DNA origami nanostructures and the positively charged peptide. Most intriguingly, the influence of the DNA origami nanostructures on hIAPP aggregation differed from that of genomic double-stranded DNA (dsDNA) and appeared to depend on DNA origami superstructure. DNA origami nanostructures may thus represent a novel route for modulating amyloid aggregation in vivo.
人胰岛淀粉样多肽（hIAPP）的聚集在2型糖尿病（T2DM）的发病机制中起主要作用，到目前为止，人们已经研究了许多控制hIAPP聚集的策略。特别是，几种有机和无机纳米颗粒（NPs）已显示出影响hIAPP以及其他淀粉样蛋白和肽聚集的潜力。除了传统的纳米颗粒外，DNA纳米结构越来越受到生物医学领域的关注。因此，在这项工作中，我们研究了两种不同的DNA折纸纳米结构对hIAPP聚集的影响。为此，我们采用了原位浊度测量和非原位原子力显微镜（AFM）。浊度测量显示DNA纳米结构对hIAPP聚集有抑制作用，而AFM结果表明hIAPP与DNA折纸纳米结构共聚集形成混合肽-DNA聚集体。我们认为这是由带负电荷的DNA折纸纳米结构与带正电荷的肽之间的强静电相互作用引起的。最有趣的是，DNA折纸纳米结构对hIAPP聚集的影响与基因组双链DNA（dsDNA）不同，似乎取决于DNA折纸超结构。因此，DNA折纸纳米结构可能代表了一种在体内调节淀粉样蛋白聚集的新途径。
