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

• Published in: Nature communications Vol. 9; no. 1; pp. 1521 - 12
• Main Authors: Birkholz, Oliver, Burns, Jonathan R., Richter, Christian P., Psathaki, Olympia E., Howorka, Stefan, Piehler, Jacob
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.04.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14/28; 14/63; 631/57/2270; 631/57/2282; 631/92/552; 639/925/926/1049; Biological activity; Cell Membrane - metabolism; Cholesterol; Cholesterol - chemistry; Cytoskeleton; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; Fabrication; Fluorescence; Fluorescence microscopy; Humanities and Social Sciences; Lipid bilayers; Lipid Bilayers - chemistry; Lipid membranes; Lipids; Lipids - chemistry; Membrane Lipids - metabolism; Membranes; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Fluorescence; multidisciplinary; Nanopores; Nanostructures - chemistry; Nanotechnology; Nanotechnology devices; Nanotubes; Piercing; Polymers - chemistry; Pores; Porosity; Replicating; Science; Science (multidisciplinary); Synthetic Biology
• ISSN: 2041-1723; 2041-1723
• 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. 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.