title: Adsorption of DNA onto anionic lipid surfaces.
abstract: Currently self-assembled DNA delivery systems composed of DNA multivalent cations and anionic lipids are considered to be promising tools for gene therapy. These systems become an alternative to traditional cationic lipid-DNA complexes because of their low cytotoxicity lipids. However, currently these nonviral gene delivery methods exhibit low transfection efficiencies. This feature is in large part due to the poorly understood DNA complexation mechanisms at the molecular level. It is well-known that the adsorption of DNA onto like charged lipid surfaces requires the presence of multivalent cations that act as bridges between DNA and anionic lipids. Unfortunately, the molecular mechanisms behind such adsorption phenomenon still remain unclear. Accordingly a historical background of experimental evidence related to adsorption and complexation of DNA onto anionic lipid surfaces mediated by different multivalent cations is firstly reviewed. Next, recent experiments aimed to characterise the interfacial adsorption of DNA onto a model anionic phospholipid monolayer mediated by Ca(2+) (including AFM images) are discussed. Afterwards, modelling studies of DNA adsorption onto charged surfaces are summarised before presenting preliminary results obtained from both CG and all-atomic MD computer simulations. Our results allow us to establish the optimal conditions for cation-mediated adsorption of DNA onto negatively charged surfaces. Moreover, atomistic simulations provide an excellent framework to understand the interaction between DNA and anionic lipids in the presence of divalent cations. Accordingly,our simulation results in conjunction go beyond the macroscopic picture in which DNA is stuck to anionic membranes by using multivalent cations that form glue layers between them. Structural aspects of the DNA adsorption and molecular binding between the different charged groups from DNA and lipids in the presence of divalent cations are reported in the last part of the study. Although this research work is far from biomedical applications, we truly believe that scientific advances in this line will assist, at least in part, in the rational design and development of optimal carrier systems for genes and applicable to other drugs.
authors.affiliation: Departamento de Física Aplicada, Universidad de Granada, Campus de Fuentenueva sn, 18071 Granada, Spain. Electronic address: almartin@ugr.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martín-Molina
authors.affiliation: Departamento de Física Aplicada, Universidad de Granada, Campus de Fuentenueva sn, 18071 Granada, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Luque-Caballero
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus de la UAB, E-08193 Bellaterra, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Faraudo
authors.affiliation: Departamento de Física, Escuela Politécnica Superior de Linares, Universidad de Jaén, 23700 Linares, Jaén, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Quesada-Pérez
authors.affiliation: Departamento de Física Aplicada, Universidad de Granada, Campus de Fuentenueva sn, 18071 Granada, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Maldonado-Valderrama
mesh_terms: D000327:Adsorption; D004247:DNA / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D013499:Surface Properties
chemical_list: D008055:Lipids; D004247:DNA
keywords: All-atomic simulations; Coarse grain models; DNA; Gene therapy; Lipid; Lipoplex