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bioRxiv · 10.64898/2026.02.16.705827

DNA-Lipid Nanodiscs with a Polyethylene Glycol Interface

Chandrasekhar, S.·Maffeo, C.·Karanth, S.·Bricker, R.·Kabuga, J.·Schmidt, D. G.·Aksimentiev, A.·Schmidt, T. L.
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Abstract

Nanoscale bilayer mimetics such as protein or polymer-based nanodiscs are versatile tools to study the physical chemistry of lipid bilayers or the structures and functions of membrane proteins. Here, we introduce DNA-Lipid Nanodiscs (DLNs) in which the interface between hydrophobic lipids and the charged DNA is mediated through amphiphilic poly(ethylene)glycol (PEG). For this, we modified oligonucleotides with PEG and hybridized them to a single-stranded ring to form functionalized minicircles with a well-defined diameter. The center of these minicircles can be filled with a lipid bilayer through addition of detergent-solubilized lipids followed by detergent removal. Simulations reveal that the methylene groups in PEG form dynamic interactions with the acyl chains of lipids, effectively shielding the hydrophobic mismatch. As proof of concept towards incorporation of complex membrane proteins, we inserted the biotinylated transmembrane domain of synaptobrevin into these nanodiscs and bound them to streptavidin-modified quantum dots as a marker for successful incorporation. We envision these atomically precise, modular DNA scaffolds to be widely applicable in future studies of membrane proteins and nanoscale lipid membranes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/705827v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@17cfcb5org.highwire.dtl.DTLVardef@b2dd2corg.highwire.dtl.DTLVardef@d6899aorg.highwire.dtl.DTLVardef@e400c4_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Chandrasekhar, S., Maffeo, C., Karanth, S., Bricker, R., Kabuga, J., Schmidt, D. G., Aksimentiev, A., Schmidt, T. L.. 2026-02-16. DNA-Lipid Nanodiscs with a Polyethylene Glycol Interface. https://doi.org/10.64898/2026.02.16.705827

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