Chromatin-like beads-on-string structure of DNA-dendrimer complex

Cationic dendrimers are a potential nonviral vector for gene therapy because of their ability to form electrostatic complexes with DNA as well as their lack of immunogenicity. The structure of the complexes can influence their interactions with cells and hence the transfection efficiency; however, the supramolecular structure of DNA-dendrimer complexes (dendriplexes) formed under different conditions remain to be explored in detail. Through the capability of SAXS and SANS for resolving the spatial organization of DNA and dendrimer in the dendriplex, respectively, here we show that the complexes of DNA with poly(amidoamine) (PAMAM) G4 dendrimer exhibited three distinct supramolecular structures modulated by the charge density of the dendrimer prescribed by its average degree of protonation (dp, the average number fraction of protonated amine groups in dendrimer) in pure water. At dp = 0.1 the dendriplex showed a columnar mesophase in which the relatively straightened DNA chains packed in a long-range ordered square lattice. Increasing dendrimer dp to 0.3 induced a moderate twisting of DNA chains into superhelices to enhance the charge matching with dendrimer and these superhelices were found to organize in a hexagonal lattice. DNA eventually wrapped around the dendrimer with a regular pitch length of ca. 3 nm forming the so-called "beads-on-string structure", when the electrostatic attraction well dominated the DNA bending energy at high dendrimer dp (dp≥ 0.6). This beads-on-string configuration is reminescent of the structure of chromatin composing of nucleosome particles each formed by wrapping ca. 147 bp DNA around an octamer of histone driven by electrostatic complexation. Therefore, DNA-dendrimer complex may be able to serve as a synthetic model system for understanding the compaction phenomenon of geonmic DNA in cell nucleus.