Membrane nanopores are key for molecular transport in biology, portable DNA sequencing^1,2,3,4, label-free single-molecule analysis^{5,6,7,8,9,10,11,12,13,14} and nanomedicine⁵. Transport traditionally relies on barrel-like channels of a few nanometres width, but there is considerable scientific and technological interest for much wider structures of tunable shape. Yet, these nanopores do not exist in nature and are challenging to build using existing de novo routes for proteins^10,15,16,17. Here, we show that rational design with DNA can drastically expand the structural and functional range of membrane nanopores. Our design strategy bundles DNA duplexes into pore subunits that modularly arrange to form tunable pore shapes and lumen widths of up to tens of nanometres. Functional units for recognition or signalling can be optionally attached. By dialling in essential parameters, we demonstrate the utility and potential of the custom-engineered nanopores by electrical direct single-molecule sensing of 10-nm-sized proteins using widely used research and hand-held analysis devices. The designer nanopores illustrate how DNA nanotechnology can deliver functional biomolecular structures to be used in synthetic biology, single-molecule enzymology and biophysical analysis, as well as portable diagnostics and environmental screening.

膜纳米孔是生物学中分子转运、便携式 DNA 测序^{1、2、3、4}、无标记单分子分析^{5、6、7、8、9、10、11、12、13、14}和纳米医学⁵的关键. 传输传统上依赖于几纳米宽的桶状通道，但对于更宽的可调谐形状结构具有相当大的科学和技术兴趣。然而，这些纳米孔在自然界中并不存在，并且很难使用现有的蛋白质从头路线构建^10,15,16,17. 在这里，我们展示了 DNA 的合理设计可以极大地扩展膜纳米孔的结构和功能范围。我们的设计策略将 DNA 双链体捆绑到孔子单元中，这些孔子单元模块化排列以形成可调节的孔形状和高达数十纳米的管腔宽度。可以选择性地附加用于识别或发信号的功能单元。通过拨入基本参数，我们通过使用广泛使用的研究和手持分析设备对 10 纳米大小的蛋白质进行电直接单分子传感，展示了定制设计的纳米孔的效用和潜力。设计师纳米孔展示了 DNA 纳米技术如何提供功能性生物分子结构，用于合成生物学、单分子酶学和生物物理分析，以及便携式诊断和环境筛查。