RT Journal Article
SR Electronic
T1 DNA-Encircled Lipid Bilayers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 285957
DO 10.1101/285957
A1 Katarina Iric
A1 Madhumalar Subramanian
A1 Jana Oertel
A1 Nayan P. Agarwal
A1 Michael Matthies
A1 Xavier Periole
A1 Thomas P. Sakmar
A1 Thomas Huber
A1 Karim Fahmy
A1 Thorsten-Lars Schmidt
YR 2018
UL http://biorxiv.org/content/early/2018/03/21/285957.abstract
AB Lipid bilayers and lipid-associated proteins play a crucial role in biology. As in vivo studies and manipulation are inherently difficult, several membrane-mimetic systems have been developed to enable investigation of lipidic phases, lipid-protein interactions, membrane protein function and membrane structure in vitro. Controlling the size and shape, or site-specific functionalization is, however, difficult to achieve with established membrane mimetics based on membrane scaffolding proteins, polymers or peptides. In this work, we describe a route to leverage the unique programmability of DNA nanotechnology and create DNA-encircled bilayers (DEBs), which are made of multiple copies of an alkylated oligonucleotide hybridized to a single-stranded minicircle. To stabilize the hydrophobic rim of the lipid bilayer, and to prevent formation of lipid vesicles, we introduced up to 2 alkyl chains per helical that point to the inside of the toroidal DNA ring and interact with the hydrophobic side chains of the encapsulated lipid bilayer. The DEB approach described herein provides unprecedented control of size, and allows the orthogonal functionalizations and arrangement of engineered membrane nanoparticles and will become a valuable tool for biophysical investigation of lipid phases and lipid-associated proteins and complexes including structure determination of membrane proteins and pharmacological screenings of membrane proteins.