Molecular Structure of Single DNA Complexes with Positively Charged Dendronized Polymers Illdiko Go ¨ ssl, † Lijin Shu, ‡ A. Dieter Schlu ¨ ter,* ,‡ and Ju ¨ rgen P. Rabe* ,† Contribution from the Department of Physics, Humboldt UniVersity Berlin, 10099 Berlin, Germany, and Institute of Chemistry, Free UniVersity Berlin, Takustrasse 3, 14195 Berlin, Germany Received December 20, 2001 Abstract: Positively charged dendronized polymers with protonated amine groups at the periphery and different dendron generations are cylindrically shaped nanoobjects whose radii and linear charge densities can be varied systematically. These polyelectrolytes have been complexed with DNA and subsequently adsorbed on precoated mica substrates. The analysis of scanning force microscopy data indicates that DNA wraps around the dendronized polymers. The calculated pitch is 2.30 ( 0.27 and 2.16 ( 0.27 nm for DNA wrapped around dendronized polymers of generation two and four, respectively. The complex with the second generation has been shown to be negatively charged, which is consistent with the theory of spontaneous overcharging of macro-ion complexes, when the electrostatic contribution to the free energy dominates over the elastic energy. The complexes may be of interest for the development of nonviral gene delivery systems. Introduction In viruses and cells, DNA is organized in tightly packed structures. Much research has been carried out in order to obtain insight into the mechanisms of condensation and aggregation of DNA, 1 which both can be induced in vitro by a variety of positive ions, due to electrostatic interactions with the oppositely charged phosphate groups on the DNA backbone. DNA molecules condense into toroids and rods in the presence of multivalent cations 2 or polyamines 3 (polyplexes), but the result- ing structures were not resolved on the molecular level. Also in complexes formed with cationic polymers 4,5 and cationic dendrimers, 6 the molecular structure remains unclear, while X-ray diffraction on complexes formed from DNA and cationic lipids 7 (lipoplexes) reveals multilammellar structures. Most of the synthetic cationic agents forming these complexes and aggregates are developed for potential use as DNA vectors in novel gene therapies. An example is the spherical poly- (amidoamine) (PAMAM) dendrimer. 8 The structure of its complex with DNA can influence the in vivo interactions with the biological material and therefore affect the efficiency of transfection, which depends in particular on the structure, size, and charge density of the dendrimers. 9 However, again, the structure of this self-assembled nonviral gene delivery system is not well understood. 10 On the other hand, a well-known ordered structure of compacted DNA is found in the nucleus of eukaryotic cells, where the DNA is associated with histone proteins to form the chromatin. X-ray crystallography has shown that, within the nucleosome, the smallest unit of the chromosome, 146 bp DNA wraps in 1.65 turns around the histone octamers 11 like a thread around a spool. Interestingly, the nucleosomal core particles have a net negative charge because the negative charge of the wrapped DNA is significantly larger than the total positive charge of the histone protein octamer. 12,13 Aside from the biological and medical aspects, the molecular structure of polyelectrolyte complexes may be used to improve our general understanding of polyelectrolyte interactions. Poly- electrolyte adsorption on charged flat surfaces or spheres (i.e., layer-by-layer adsorption 14 ) has been a focus in experimental and theoretical studies. 15,16 Also, theoretical models of the * To whom correspondence should be addressed. A.D.S.: phone, +49- 30-838 53358; fax, +49-30-838 53357; E-mail, adschlue@chemie.fu- berlin.de. J.P.R.: phone, +49-30-2093 7788; fax, +49-30-2093 7632; E-mail, rabe@physik.hu-berlin.de. † Humboldt University Berlin. ‡ Free University Berlin. (1) Bloomfield, V. A. Biopolymers 1991, 31, 1471. (2) Hud, N. V.; Downing, K. H.; Balhorn, R. Proc. Natl. Acad. Sci. 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D.; Felsenfeld, G. Nucleic Acids Res. 1980, 8, 2751. (14) Decher, G. Science 1997, 277, 1232. (15) Caruso, F.; Lichterfeld, H.; Donath, E.; Mo ¨hwald, H. Macromolecules 1999, 32, 2317. (16) Netz, R. R.; Joanny, J.-F. Macromolecules 1999, 32, 9013 & 9026. Published on Web 05/24/2002 6860 9 J. AM. CHEM. SOC. 2002, 124, 6860-6865 10.1021/ja017828l CCC: $22.00 © 2002 American Chemical Society