Aug 2026· ACS Nano· Vol 20 32, pp.
22909-22918
· 0 citations· 43 references
Medicine
Abstract
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.
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Bacterial contractile injection systems provide a model for membrane penetration and targeted delivery of molecular cargo through mechanical actuation. Replicating these features in synthetic nanoscale systems remains challenging, particularly with respect to coupling structural organization with dynamic actuation, rev...
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Vesicles formed from amphiphilic copolymers, alone or blended with phospholipids, offer superior mechanical and chemical stability compared to conventional lipid vesicles. This makes them an attractive chassis, one that can be further developed and expanded to enable specific applications, such as drug delivery, diagno...
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