DNA-encircled lipid bilayer: a nano-scaled membrane-mimetic system

Lipid bilayers and lipid-associated proteins play a crucial role in biology. Since studies and manipulation in vivo are inherently challenging, several in vitro membrane-mimetic systems have been developed to enable the study of lipidic phases, lipid-protein interactions and membrane protein function. Controlling the size and shape or introducing functional elements in a programmable way is, however, difficult to achieve with common systems based on polymers, peptides or membrane scaffolding proteins. In this work we describe a route leveraging the unique programmability of DNA nanotechnology to create DNA-encircled bilayers (DEBs) as a novel nano-scaled membrane-mimetic. For this, alkylated oligonucleotides are hybridized to a single-stranded minicircle (ssMC) such that all alkyl chains point to the inside stabilizing the lipid bilayer. Atomic force microscopy (AFM), transmission electron microscopy (TEM) and coarse grain molecular dynamics (CGMD) simulations confirm the formation of discoidal lipid bilayer structures. Fluorescence spectroscopy was used to monitor lipid phase transitions and revealed head group-dependent lipid-DNA interactions at the bilayer rim. The DEB technology described herein provides unprecedented control of size, shape, stability and functionalization of engineered membrane nanoparticles and will become a valuable tool for biophysical investigation of lipid phases and lipid-associated proteins and complexes.