Cation and buffer specific effects on the DNA-lipid interaction

Mura, Monica;Humphreys, Ben;Gilbert, Jennifer;Salis, Andrea

;Nylander, Tommy

2023-01-01

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Abstract

Knowledge of DNA - lipid layer interactions is key for the development of biosensors, synthetic nanopores, scaffolds, and gene-delivery systems. These interactions are strongly affected by the ionic composition of the solvent. We have combined quartz crystal microbalance (QCM) and ellipsometry measurements to reveal how pH, buffers and alkali metal chloride salts affect the interaction of DNA with lipid bilayers (DOTAP/DOPC 30:70 in moles). We found that the thickness of the DNA layer adsorbed onto the lipid bilayer decreased in the order citrate > phosphate > Tris > HEPES. The effect of cations on the thickness of the DNA layer decreased in the order (K+ > Na+ > Cs+ ∼ Li+). Rationalization of the experimental results requires that adsorption, due to cation specific charge screening, is driven by the simultaneous action of two mechanisms namely, the law of matching water affinities for kosmotropes (Li+) and ion dispersion forces for chaotropes (Cs+). The outcome of these two opposing mechanisms is a “bell-shaped” specific cations sequence. Moreover, a superimposed buffer specificity, which goes beyond the simple effect of pH regulation, further modulated cation specificity. In summary, DNA-lipid bilayer interactions are maximized if citrate buffer (50 mM, pH 7.4) and KCl (100 mM) are used.