Zhao, Z. et al. J. Am. Chem. Soc. 140, 10639–10643 (2018).
Phospholipid-bilayer nanodiscs are model membrane systems that offer a native-like environment for the study of membrane proteins. However, the size of such synthetic bilayer nanodiscs is generally limited to less than 20 nm in diameter, which hinders their application with large membrane proteins. To address this limitation, Zhao et al. used a DNA origami scaffold to assist in the formation of stable nanodiscs with a diameter of ~70 nm. They used a DNA origami barrel as a scaffolding corral to recruit a number of small (~11 nm) nanodiscs, and then used detergent to induce local rearrangement of the adjacent bilayers, thus allowing neighboring nanodiscs to merge and form one interconnected structure. The flexibility of the DNA origami scaffold and excess lipids are required for the formation of large, circular, bilayer nanodiscs. The enclosed nanodiscs are relatively stable and tolerant to a broad range of pH levels and divalent ion concentrations. The researchers applied this nanodisc system to reconstitute two membrane-protein clusters and to study poliovirus entry.