Stern-Layer Adsorption of Oligonucleotides on Lamellar Cationic Lipid Bilayer Investigated by Polarization-Resolved SFG-VS

[Image: see text] The molecular interaction between the oligonucleotides and lipid membranes is the key to the functions of virus, aptamer, and various oligonucleotide-based materials. In this study, the conformational changes of oligonucleotides (dT(25)) on lamellar cationic 1,2-dimyristoyl-3-trimethylammonium-propane (DMTAP) bilayer were investigated by polarization-resolved sum frequency generation vibrational spectroscopy (SFG-VS) in situ. The SFG-VS spectra within different wavenumber ranges were analyzed to give conformation details of thymine groups, phosphate groups, and OD/OH groups and to provide a comprehensive and fundamental understanding of the oligonucleotide adsorption on a model bilayer. It is shown that the adsorption of dT(25) on DMTAP bilayer reaches maximum at C(dT) ≈ 500 nM. And the conformation of dT(25) molecules change significantly when surface charge of DMTAP bilayer reaches the point of zero charge (PZC) at C(dT) ≈ 100 nM. Combined spectroscopic evidences also indicate that the formation of electric double layer at the DMTAP/dT(25) surface follows the Gouy–Chapman–Stern model. The analysis results also show that the symmetric PO(2)(–) stretching mode of oligonucleotide molecules can serve as a sensitive vibration molecular probe for quantifying the oligonucleotide/lipid charge ratio and determine the point of zero charge (PZC) of lipid bilayer surface, which may help researchers to control the layer-by-layer assembly of oligonucleotide–lipid complexes and to improve the efficiency genetic therapy against cancer and viral infections.