Soft Report - Dipartimento di Fisica - Sapienza

Scientific Report – Self Assembly, Clustering, Structural arrestCoil-Globule Transition of DNA Molecules Induced byCationic SurfactantsCompaction of DNA induced by cationic surfactantshave attracted in the recent years a large amount ofinterest due to its importance both in technologicaland biomedical applications, particularly for thepotential use of these systems as vehicles for genedelivery and gene transfection. One of limitingfactors for gene therapy is the DNA transport, since,under normal physiological condition, DNA is a highlycharged polyion that is repelled by the similarlynegative cell membrane.In the complexation between DNA and cationicspecies, the effective negative charge of DNA islowered, allowing the complex to approach thecharged cell membrane. In addition, it has beenshown that cationic surfactants collapse individualDNA molecules and lead to small particles allowingan efficient internalization of these complexes intothe cells. In relation to this, the DNA inchromosomes was found to be in a highly condensedstate in comparison with the free DNA in thesolution.A wide variety of physical methods have beenapplied to the study of DNA-surfactant interactionsand recently these interactions have been alsostudied at the single-molecule level, with the use ofa fluorescent microscopy technique [1,2].It has been found that isolated DNA chains undergoa discrete coil-globule transition by the addition ofcationic surfactants, with a region where coil andglobule form coexist for intermediate concentrationof amphiphile. The molecular mechanism leading tothis conformational change has been described asfollows. Cationic surfactants interact with DNA by acombination of initial electrostatic interactionfollowed by a cooperative binding of surfactantligands to the same DNA molecule, driven byhydrophobic forces. The coexistence of DNAmolecules with different conformation has only beenobserved, to our knowledge, by fluorescencemicroscopy.Recently, we used dynamic light scattering [3] anddielectric spectroscopy [4] to investigate thecompaction of DNA induced by two simple modelamphiphiles, cetyltrimethylammonium bromide(CTAB), a single chain cationic surfactant, anddodecyldimethylamine oxide (DDAO), which cancoexist in either non ionic or cationic form,depending on pH. The behaviour of thehydrodynamic radius and the size distribution of theDNA-surfactant complexes have been studieddirectly by dynamic light scattering, evidencing abimodal distribution with the simultaneous presenceof coil and compact globule state, whose relativeconcentration changes with the surfactantconcentration (see Fig.1)This clearly shows that coil and globule form coexistin the surfactant solution at a concentration intervalin which the cooperative continuous transition isobserved in the macroscopic ensemble of DNAchains. It is the first time, to our knowledge, that thecoil-globule coexistence is observed in bulk, in adirect way. The overall phenomenology observed forCTAB and DDAO surfactants is quite similar,although, in the latter one, the pH-induced degree ofprotonation is small. This finding clearly indicates theimportant role of the hydrophobic interactions in theformation of DNA-surfactant complex.References[1] S.M. Mel'nikov, V.G. Sergeyev, K. Yoshikava, J.Am. Chem. Soc., 117, 2401, (1995).[2] Y.S. Mel'nikova, B. Lindman, Langmuir , 16,5871, (2000).[3] S.Marchetti, G. Onori, C. Cametti, Journal ofPhysical Chemistry B., 109, 3676, (2005).[4] A. Bonincontro. S. Marchetti, G. Onori, A. Rosati,Chem. Phys., 312, 55, (2005).Fig. 1: Average hydrodynamic diameter 2R H of DNA-CTAB complexes as a function of the surfactant toDNA-phosphate molar charge ratio X. The insetshows the size distribution at two different values ofX, before and close to the neutralization condition,X=0.55, where there is a bimodal distribution andX=1.22, where only a monomodal distributionappears.AuthorsG. Onori (a), S. Marchetti (a), C. Cametti (b)(a) Dipartimento di Fisica, Università di Perugia andCEMIN and INFM-CRS SOFT, Unità di Roma 1.(b) Dipartimento di Fisica, Università di Roma « LaSapienza », Piazzale A. Moro 5, I-00185- Roma(Italy) and INFM- CRS SOFT, Unità di RomaSOFT Scientific Report 2004-0694