J. Am. Chem. SOC. 1995,117, zyxwvu 2401-2408 240 zy 1 Discrete Coil-Globule Transition of Large DNA Induced by Cationic Surfactant Sergey M. Mel'nikov? Vladimir G. SergeyevJ and Kenichi Yoshikawa*" Contribution from the Division of Informatics for Natural Sciences, Graduate School of Human Informatics, Nagoya University, Nagoya 464-01, Japan, and Department zyx of Polymer Science, Faculty of Chemistry, Moscow State University, Moscow 119899, Russia Received October 18, 1994@ Abstract: It becomes clear that large DNA molecules exhibit discrete conformational change between the coil and globule states with the addition of a very small amount (with the order of M) of cationic surfactant, cetyltrimethylammoniumbromide (CTAB). We use fluorescence microscopy zyxwv as a tool of single molecular observation of double-stranded T4DNA in an aqueous environment. When the concentration of CTAB is less than 9.4 x M, all DNA molecules exhibit the extended coil state. Whereas, when the CTAB concentration is higher than 2.0 x M, only compacted DNA molecules in the globular state are observed. In the region between these two critical concentrations, the coil and globule states coexist in the solution. A small but apparent increase of the size of the DNA globule is noticed at the CTAB concentration higher than M, due to the penetration of CTAB molecules into the DNA globule. To study the dynamical aspect of coil-globule transition, the process of the structural change from the coil into the globule state is observed under the spatial gradient of the CTAB concentration. The formation of aggregates from two or more globules is noticed at high concentrations of surfactant above 1.6 x M. Below this concentration, the globules do not coalesce into an aggregate even if they collide with each other. The translational diffusion constant D of DNA molecules is measured from the time series of video frames of the fluorescence image. The hydrodynamic gyration radius is evaluated from the D and the viscosity of the bulk aqueous solutions. The increase of the globule size at the higher CTAB concentrations above M is confiied by the increase of & values. Introduction It is ~ell-established'-~ that in a living cell, the information stored as the base sequence along the DNA chain is expressed as the production of a rich variety of proteins in a self-regulatory manner. Thus, it is expected that the interaction of DNA with various kinds of chemical components in a cell, such as proteins, lipids, and inorganic ions, is essentially important in the regulation of a living state. Interactions between ionic surfac- tants and polyions with the opposite charge lead to the formation of polymer-colloid complexes$-8 in which the polyelectrolyte chain binds with surfactant molecules through Coulomb attrac- tive interaction, and the hydrophobic moieties of the surfactant molecules may stabilize the complexes due to the hydrophobic interactions in aqueous solution. The formation of polymer- colloid complexes induces a conformational change in the * Author to whom all correspondence should be addressed. t The permanent address of S.M.M. and the present address of V.G.S.: Department of Polymer Science, Faculty of Chemistry, Moscow State Universitv. Moscow. Russia. Nagdya University. @Abstractoublished in Advance ACS Abstracts, February 15, 1995. (1) Alberts: B.; Bray, D.; Lewis, J.; Raff, M.; Roberts, K.; Watson, J. D. Molecular Biology of the Cell; Garland Publishing, Inc.: New York, 1989. (2) Lewin, B. Genes zyxwvutsrqponm V; Oxford University Press: Oxford, 1994. 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In relation to this, the DNA in bacterial nucleotides and chromosomes was found to be in a highly condensed state in comparison with the free DNA in the sol~tion.~-'~ Cationic lipids are known as efficient nonviral reagents to transfect outer DNA into animal cells in vitro.l3 Although cationic surfactants are widely used as effective germicidal chemical^,'^ physicochemical studies on the interac- tion of cationic surfactants with DNA seem to have been rather few. In this paper, we use fluorescence microscopy for the study of the conformational change of the double-stranded DNA molecules induced by surfactant ions. During the past decade, fluorescence microscopy has been applied both for the study of the conformational change of DNA molecules in the presence of synthetic hydrophilic polymers's,'6 and various types of fluorescent dyes1'J8 and for the analysis of relaxati~n'~ and tube- like motion20 of single DNA molecules. 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E.; Chu, S. Science 1994, 264, 822-826. (20) Perkins, T. T.; Smith, D. E.; Chu, S. Science 1994,264, 819-822. 0002-7863/95/1517-2401$09.00/0 0 1995 American Chemical Society