Structural polymorphism of DNA-dendrimer complexes

DNA condensation in vivo relies on electrostatic complexation with small cations or large histones. We report a synchrotron x-ray study of the phase behavior of DNA complexed with synthetic cationic dendrimers of intermediate size and charge. We encounter unexpected structural transitions between columnar mesophases with in-plane square and hexagonal symmetries, as well as liquidlike disorder. The isoelectric point is a locus of structural instability. A simple model is proposed based on competing long-range electrostatic interactions and short-range entropic adhesion by counterion release.

Figure 1

(a),(b) X-ray scans as a function of the PPI-DNA charge ratio $N/P$ for $G4$-DNA (a) and $G5$-DNA (b) complexes. Dashed line in (a) is the scattering profile for a DNA/small-cation hexagonal bundle ($H^{\prime }$ phase, $10\mathrm{m}M$ spermidine). The ratio $q_1/q_0$ equals $\sqrt{2}$ for square symmetry ($S$ phase) and $\sqrt{3}$ for hexagonal symmetry ($H$ phase). (c) Lattice constants of the $G4$-DNA (bottom) and $G5$-DNA (top) complexes as a function of $N/P$. Dark gray bars indicate the isoelectric point. The light gray bar indicates the $S$-to-$H$ phase transition.

Figure 2

Cross-polarized microscopy of $G4$-DNA complexes with $N/P=10$. The individual threads consist of aligned columnar condensates (scale bar 0.1 mm).

Figure 3

Quasi-2D unit cells. DNA rods are drawn as helices. Dendrimers (solid circles) are centered on the symmetry sites of the interstitial regions for the (a) $S$ and (b) $H$ phases of $G4$. The $H$ phase contains two dendrimer columns per unit cell; the staggered arrangement is hypothetical.

Figure 4

X-ray scans of $G4$-DNA complexes with NaCl. (a) For $75\mathrm{m}M$, the $S$-to-$H$ transition is shifted to a higher $N/P$ value than without salt. The lattice constant increases with $N/P$. (b) For $100\mathrm{m}M$, the $S$ phase remains stable but long-range, in-plane positional order of the $H$ phase is lost. (c) For $200\mathrm{m}M$, the melting transition takes place earlier ($N/P=8$). (d) The full phase diagram as a function of salt concentration and $N/P$ ratio.