Membrane-Spanning DNA Nanopores. Biomimetic Chemical Structures for Single-Molecule Research and Nanotechnology

DNA nanotechnology excels at rationally designing bottom-up structures that can functionally replicate naturally occurring proteins. We describe the design and generation of stable self-assembled DNA-based nanopores that functionally mimic membrane protein pores and insert into lipid bilayers to support transmembrane water flow. The DNA nanopores consist of a bundle of six hexagonally arranged duplexes which are interconnected by cross-overs. The negatively charged nanobarrels carry lipid anchors to facilitate the pores' insertion into the hydrophobic bilayers. The lipid anchors either neutralize localized negative charges on the DNA backbone to create a hydrophobic belt to resemble amphiphilic protein pores, as demonstrated with alkylated phosphorothioate groups (Nano Letters, 2013, 13, 2351). Alternatively, anchoring can be achieved with few, large hydrophobic group such as porphyrin which doubles as fluorophore (Angew Chem, doi anie.201305765, Front Cover). The nanoarchitectures are correctly assembled as confirmed by AFM, SEC, and DLS, and are fully functional as shown by single-channel current recordings. The small membrane-spanning DNA pores merge the fields of nanopores and DNA-nanotechnology and will help open up the design of entirely new molecular devices for applications within single-molecule research and sensing, electric circuits, catalysis, and nanofluidics.