Gevers, JulietteJulietteGeversMartens, KoenKoenMartensFauvart, MaartenMaartenFauvartVanuytsel, StevenStevenVanuytselCarrera I Cardona, GerardGerardCarrera I CardonaLucas, FlorianFlorianLucasVelpula, GangamallaiahGangamallaiahVelpulaDe Feyter, StevenStevenDe FeyterDedecker, PeterPeterDedeckerMaglia, GiovanniGiovanniMagliaVan Dorpe, PolPolVan Dorpe2026-09-102026-09-1020261936-08511936-086Xhttps://imec-publications.be/handle/20.500.12860/60306<jats:title>Abstract</jats:title> <jats:p>Membrane proteins are central to cellular function and constitute the majority of drug targets, yet their structural and functional characterization at the single-molecule level requires stabilization within a native-like lipid environment. Here, we introduce a robust and tunable DNA origami nanodisc that incorporates inherently planar lipid bicelles as a promising platform for future membrane protein studies. The highly charged and bulky DNA envelope acts as a structural stabilizer, enabling efficient bicelle incorporation and stabilization. Moreover, bilayer geometry can be precisely tuned by adjusting the long-chain to short-chain lipid ratio (q-ratio), yielding diameters from ∼18 to 26 nm. As a proof of concept, we demonstrate the successful association of Fragaceatoxin C (FraC) monomers, a pore-forming membrane protein, with the DNA-stabilized bicelles. Potential applications of this versatile platform include high-throughput membrane protein analysis, hydrophobic drug delivery, and hybrid nanopore sensing.</jats:p>engJournal article10.1021/acsnano.6c09188WOS:001845059600001PHOSPHORUS NMRNANOSTRUCTURESBICELLESLIPOSOMESPROTEINSPLATFORMSIZEMEDLINE:426112541936-086X