Control of Membrane Binding and Diffusion of Cholesteryl-Modified DNA Origami Nanostructures by DNA Spacers
Control of Membrane Binding and Diffusion of Cholesteryl-Modified DNA Origami Nanostructures by DNA Spacers
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DOI：
10.1021/acs.langmuir.8b01850
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发表时间：
2018-12-11
期刊：
影响因子：
3.9
通讯作者：
Schwille, Petra
中科院分区：
文献类型：
--
作者：
Khmelinskaia, Alena;Muecksch, Jonas;Schwille, Petra
DNA折纸纳米技术正越来越多地用于模拟膜相关的生物物理现象。尽管已经产生了多种DNA折纸纳米结构以靶向脂质膜，但膜结合的要求迄今尚未得到系统评估。在这里，我们使用了一组具有不同位置和数量的胆固醇基膜锚的细长DNA折纸结构，以比较其掺入的不同策略。使用不同长度的单链和双链DNA间隔区将单个和多个胆固醇锚连接到DNA纳米结构。所产生的DNA纳米结构的膜结合和扩散方面进行了研究。我们的研究结果表明，锚定部分的位置和数量起着至关重要的作用，膜结合的DNA纳米结构，主要是如果胆固醇锚是在接近庞大的DNA纳米结构。此外，DNA间隔区的使用在很大程度上克服了局部空间位阻，从而增强了膜结合。荧光相关光谱测量表明，单链和双链DNA间隔子的不同物理性质控制着两亲性DNA纳米结构与脂质膜的相互作用。因此，我们提供了一个合理的基础设计的两亲性DNA折纸纳米结构，有效地结合在各种环境中的脂质膜。
DNA origami nanotechnology is being increasingly used to mimic membrane-associated biophysical phenomena. Although a variety of DNA origami nanostructures has already been produced to target lipid membranes, the requirements for membrane binding have so far not been systematically assessed. Here, we used a set of elongated DNA origami structures with varying placement and number of cholesteryl-based membrane anchors to compare different strategies for their incorporation. Single and multiple cholesteryl anchors were attached to DNA nanostructures using single- and double-stranded DNA spacers of varying length. The produced DNA nanostructures were studied in terms of their membrane binding and diffusion. Our results show that the location and number of anchoring moieties play a crucial role for membrane binding of DNA nanostructures mainly if the cholesteryl anchors are in close proximity to the bulky DNA nanostructures. Moreover, the use of DNA spacers largely overcomes local steric hindrances and thus enhances membrane binding. Fluorescence correlation spectroscopy measurements demonstrate that the distinct physical properties of single- and double-stranded DNA spacers control the interaction of the amphipathic DNA nanostructures with lipid membranes. Thus, we provide a rational basis for the design of amphipathic DNA origami nanostructures to efficiently bind lipid membranes in various environments.