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Issue 16, 2014
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Using AFM to probe the complexation of DNA with anionic lipids mediated by Ca2+: the role of surface pressure

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Abstract

Complexation of DNA with lipids is currently being developed as an alternative to classical vectors based on viruses. Most of the research to date focuses on cationic lipids owing to their spontaneous complexation with DNA. Nonetheless, recent investigations have revealed that cationic lipids induce a large number of adverse effects on DNA delivery. Precisely, the lower cytotoxicity of anionic lipids accounts for their use as a promising alternative. However, the complexation of DNA with anionic lipids (mediated by cations) is still in early stages and is not yet well understood. In order to explore the molecular mechanisms underlying the complexation of anionic lipids and DNA we proposed a combined methodology based on the surface pressure–area isotherms, Gibbs elasticity and Atomic Force Microscopy (AFM). These techniques allow elucidation of the role of the surface pressure in the complexation and visualization of the interfacial aggregates for the first time. We demonstrate that the DNA complexes with negatively charged model monolayers (DPPC/DPPS 4 : 1) only in the presence of Ca2+, but is expelled at very high surface pressures. Also, according to the Gibbs elasticity plot, the complexation of lipids and DNA implies a whole fluidisation of the monolayer and a completely different phase transition map in the presence of DNA and Ca2+. AFM imaging allows identification for the first time of specific morphologies associated with different packing densities. At low surface coverage, a branched net like structure is observed whereas at high surface pressure fibers formed of interfacial aggregates appear. In summary, Ca2+ mediates the interaction between DNA and negatively charged lipids and also the conformation of the ternary system depends on the surface pressure. Such observations are important new generic features of the interaction between DNA and anionic lipids.

Graphical abstract: Using AFM to probe the complexation of DNA with anionic lipids mediated by Ca2+: the role of surface pressure

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Publication details

The article was received on 15 Sep 2013, accepted on 10 Jan 2014 and first published on 10 Jan 2014


Article type: Paper
DOI: 10.1039/C3SM52428K
Citation: Soft Matter, 2014,10, 2805-2815
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    Using AFM to probe the complexation of DNA with anionic lipids mediated by Ca2+: the role of surface pressure

    G. Luque-Caballero, A. Martín-Molina, A. Y. Sánchez-Treviño, M. A. Rodríguez-Valverde, M. A. Cabrerizo-Vílchez and J. Maldonado-Valderrama, Soft Matter, 2014, 10, 2805
    DOI: 10.1039/C3SM52428K

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