Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure
Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure
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基于 DNA 的离子通道的膜活性取决于其双链结构的稳定性
DOI：
10.1021/acs.nanolett.1c03791
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发表时间：
2021
期刊：
影响因子：
10.8
通讯作者：
Keyser, Ulrich F.
中科院分区：
文献类型：
--
作者：
Morzy, Diana;Joshi, Himanshu;Sandler, Sarah E.;Aksimentiev, Aleksei;Keyser, Ulrich F.
DNA纳米技术已经成为设计自发插入和完全可控的合成离子通道的一种很有前途的方法。然而，现有的基于DNA的膜通道的插入效率和稳定性都有很大的改进空间。在这里，我们展示了一种克服不利的DNA-脂质相互作用的方法，这些相互作用阻碍了稳定的跨膜孔的形成。我们的全原子MD模拟和实验表明，插入驱动胆固醇的修饰可以导致缺口DNA结构的末端碱基对的磨损，当嵌入到脂质双层中时，它们会扭曲。重要的是，我们发现没有骨架不连续的DNA纳米结构形成了更稳定的导电孔，并以比同等的NiCk结构更高的效率插入到膜中。此外，由于没有刻痕，因此可以在脂质双层内设计和维护倾斜取向的跨膜螺旋。因此，减少DNA纳米结构的构象自由度可以更好地控制它们作为合成离子通道的功能。
DNA nanotechnology has emerged as a promising method for designing spontaneously inserting and fully controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based membrane channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA–lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications can cause fraying of terminal base pairs of nicked DNA constructs, distorting them when embedded in a lipid bilayer. Importantly, we show that DNA nanostructures with no backbone discontinuities form more stable conductive pores and insert into membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows design and maintenance of membrane-spanning helices in a tilted orientation within the lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.