DNA-Encircled Lipid Bilayers

Abstract

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.

Two decades of Martini: Better beads, broader scope

“…165 In this section, we focused on lipids and protein applications, which make up the bulk of the Martini studies in the literature. There have also been interesting recent applications using the nucleic acid parameters, for example, for modeling aspects of drug delivery 196,271 (Figure 5d), nucleosome formation, 272 DNA-scaffolded nanodiscs, 273,274 and 271 DNA-based nanopores, 275,276 and carbohydrates, in modeling cellulose 277 and glycosylated proteins, 60,278 and development of important biopolymers including peptidoglycans 279 for more realistic simulations of Gram-negative bacterial membranes. We expect such applications to become more prevalent as Martini 3 continues to be developed.…”