Hydrophobic Interactions between DNA Duplexes and Synthetic and Biological Membranes
| Autor: | Ulrike S. Eggert, Sioned Fôn Jones, Aleksei Aksimentiev, Stephen J. Terry, Himanshu Joshi, Stefan Howorka, Jonathan R. Burns |
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| Rok vydání: | 2021 |
| Předmět: |
Lipid Bilayers
02 engineering and technology Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Phosphates Hydrophobic effect Cell membrane chemistry.chemical_compound Colloid and Surface Chemistry medicine Lipid bilayer Molecular Structure Cell Membrane Rational design Biological membrane DNA General Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Membrane medicine.anatomical_structure chemistry Biophysics lipids (amino acids peptides and proteins) 0210 nano-technology Sphingomyelin Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Equipping DNA with hydrophobic anchors enables targeted interaction with lipid bilayers for applications in biophysics, cell biology, and synthetic biology. Understanding DNA–membrane interactions is crucial for rationally designing functional DNA. Here we study the interactions of hydrophobically tagged DNA with synthetic and cell membranes using a combination of experiments and atomistic molecular dynamics (MD) simulations. The DNA duplexes are rendered hydrophobic by conjugation to a terminal cholesterol anchor or by chemical synthesis of a charge-neutralized alkyl-phosphorothioate (PPT) belt. Cholesterol-DNA tethers to lipid vesicles of different lipid compositions and charges, while PPT DNA binding strongly depends on alkyl length, belt position, and headgroup charge. Divalent cations in the buffer can also influence binding. Our MD simulations directly reveal the complex structure and energetics of PPT DNA within a lipid membrane, demonstrating that longer alkyl-PPT chains provide the most stable membrane anchoring but may disrupt DNA base paring in solution. When tested on cells, cholesterol-DNA is homogeneously distributed on the cell surface, while alkyl-PPT DNA accumulates in clustered structures on the plasma membrane. DNA tethered to the outside of the cell membrane is distinguished from DNA spanning the membrane by nuclease and sphingomyelinase digestion assays. The gained fundamental insight on DNA–bilayer interactions will guide the rational design of membrane-targeting nanostructures. |
| Databáze: | OpenAIRE |
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