Multi-functional DNA nanostructures that puncture and remodel lipid membranes into hybrid materials.

Multi-functional DNA nanostructures that puncture and remodel lipid membranes into hybrid materials.
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DOI:
10.1038/s41467-018-02905-w
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发表时间:
2018-04-18
影响因子:
16.6
通讯作者:
Piehler J
Piehler J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Birkholz O;Burns JR;Richter CP;Psathaki OE;Howorka S;Piehler J

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合成复制关键的生物过程需要能够刺穿脂质双层膜并重塑其形状。最近开发的人工DNA纳米孔是一种可能的合成途径,因为它们易于制造。然而,一个尚未解决的基本问题是DNA纳米孔如何与脂质双层结合并动态相互作用。在这里,我们使用单分子荧光显微镜来确定携带胆固醇锚的DNA纳米孔通过两步机制插入膜中。此外,纳米孔被示出局部聚集并将膜重塑成纳米级突起。最引人注目的是,DNA孔可以通过稳定自主形成的脂质纳米管来作为细胞骨架成分。膜穿刺和重塑活性的组合可以归因于DNA孔在两个取向之间的可调转变,以跨越脂质双层或与脂质双层共对齐。这一见解有望促进合成生物学和纳米生物技术相关的未来功能性纳米器件的发展。DNA纳米孔可以跨越脂质双层,但它们如何与脂质相互作用尚不清楚。在这里,作者在单分子水平上建立了插入机制,并表明DNA纳米孔可以局部聚集和重塑膜,并稳定自主形成的脂质纳米管。
Synthetically replicating key biological processes requires the ability to puncture lipid bilayer membranes and to remodel their shape. Recently developed artificial DNA nanopores are one possible synthetic route due to their ease of fabrication. However, an unresolved fundamental question is how DNA nanopores bind to and dynamically interact with lipid bilayers. Here we use single-molecule fluorescence microscopy to establish that DNA nanopores carrying cholesterol anchors insert via a two-step mechanism into membranes. Nanopores are furthermore shown to locally cluster and remodel membranes into nanoscale protrusions. Most strikingly, the DNA pores can function as cytoskeletal components by stabilizing autonomously formed lipid nanotubes. The combination of membrane puncturing and remodeling activity can be attributed to the DNA pores’ tunable transition between two orientations to either span or co-align with the lipid bilayer. This insight is expected to catalyze the development of future functional nanodevices relevant in synthetic biology and nanobiotechnology. DNA nanopores can span lipid bilayers but how they interact with lipids is not known. Here the authors establish at single-molecule level the insertion mechanism and show that DNA nanopores can locally cluster and remodel membranes, and stabilize autonomously formed lipid nanotubes.
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