DNA with amphiphilic counterions: tuning colloidal DNA with cyclodextrin

Abstract

DNA compaction in vitro can be controlled by lipids. Cyclodextrins can disperse lipids in the form of water soluble inclusion complexes, thus tuning their self-assembly. To progress in the fundamental understanding of double-stranded (ds) DNA–lipid–cyclodextrin interactions, the aqueous phase behavior of a cationic surfactant (dodecyltrimethylammonium, DTA)–dsDNA compound in the presence of cyclodextrin (hydroxypropyl-β-cyclodextrin, HPβCD, or β-cyclodextrin, βCD) was investigated. βCD has a low water solubility due to the formation of stable crystals. The more hydrophobic HPβCD, on the other hand, is highly water soluble because the bulky HP substitution destabilizes the crystalline state. Both βCD and HPβCD form strong inclusion complexes with DTA, with an essentially infinite binding constant, and the DNA self-assembly behavior is controlled by the molar ratio R = [DTA]/[CD], in addition to the DNA concentration. DTA–DNA can be solubilized in the isotropic liquid phase of water and HPβCD when R ≤ 1. This phase is micelle free and from the sharp phase boundary at R = 1 it is concluded that HPβCD does not associate with DNA, only with DTA. Increasing the DTA–DNA concentration, keeping R < 1, leads to the formation of a liquid crystal with 2D hexagonally ordered DNA. With a further increase of the DTA–DNA and R > 1.5–2, a second, novel, anisotropic phase is formed that we identify as having a tetragonal lattice. In this phase, the DNA duplexes are still parallel but with a simple square rather than a hexagonal packing. The periodicity in the direction of the DNA duplexes is coupled to the DNA pitch length, 3.3 nm. With βCD, the phase behavior is less rich because of the poor water solubility of the cyclodextrin. Here, only a very small hexagonal phase region is formed in the center of the ternary phase diagram, with R ≈ 1.