Department of Biology and Center for Cellular Nanoanalytics (CellNanOs), University of Osnabrück, Barbarastr. 11, 49076, Osnabrück, Germany.
Department of Chemistry, Institute of Structural and Molecular Biology, University College London, 20 Gordon Street, London, WC1H OAJ, UK.
Nat Commun. 2018 Apr 18;9(1):1521. doi: 10.1038/s41467-018-02905-w.
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.
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 纳米孔由于其易于制造，是一种可能的合成途径。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与之动态相互作用。在这里，我们使用单分子荧光显微镜来建立携带胆固醇锚的 DNA 纳米孔通过两步机制插入膜的机制。还表明纳米孔局部聚集并将膜重塑成纳米尺度的突起。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作为细胞骨架成分发挥作用。膜穿孔和重塑活性的组合可以归因于 DNA 孔在跨越或与脂质双层共对准的两种取向之间的可调转变。预计这一见解将促进未来在合成生物学和纳米生物技术中具有相关功能的纳米器件的发展。
