title: Biophysical properties of cationic lipophosphoramidates: Vesicle morphology, bilayer hydration and dynamics.
abstract: Cationic lipids are used to deliver genetic material to living cells. Their proper biophysical characterization is needed in order to design and control this process. In the present work we characterize some properties of recently synthetized cationic lipophosphoramidates. The studied compounds share the same structure of their hydrophobic backbone, but differ in their hydrophilic cationic headgroup, which is formed by a trimethylammonium, a trimethylarsonium or a dicationic moiety. Dynamic light scattering and cryo-transmission electron microscopy proves that the studied lipophosphoramidates create stable unilamellar vesicles. Fluorescence of polarity probe, Laurdan, analyzed using time-dependent fluorescence shift method (TDFS) and generalized polarization (GP) gives important information about the phase, hydration and dynamics of the lipophosphoramidate bilayers. While all of the compounds produced lipid bilayers that were sufficiently fluid for their potential application in gene therapy, their polarity/hydration and mobility was lower than for the standard cationic lipid - DOTAP. Mixing cationic lipophosphoramidates with DOPC helps to reduce this difference. The structure of the cationic headgroup has an important and complex influence on bilayer hydration and mobility. Both TDFS and GP methods are suitable for the characterization of cationic amphiphiles and can be used for screening of the newly synthesized compounds.
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Loizeau
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 18223 Prague 8, Czech Republic.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jurkiewicz
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 18223 Prague 8, Czech Republic.
authors.forename: Gokcan
authors.initials: G
authors.lastname: Aydogan
authors.affiliation: Institute of Molecular Genetics of the ASCR, v.v.i., Laboratory of Biology of the Cell Nucleus, Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Anatoly A
authors.initials: AA
authors.lastname: Philimonenko
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Selim
authors.initials: S
authors.lastname: Mahfoudhi
authors.affiliation: Institute of Molecular Genetics of the ASCR, v.v.i., Laboratory of Biology of the Cell Nucleus, Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hozák
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Maroto
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Couthon-Gourvès
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Deschamps
authors.affiliation: UMR CNRS 6521, SFR 148 ScInBIoS, Université de Brest, Université Européenne de Bretagne, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Giamarchi
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 18223 Prague 8, Czech Republic. Electronic address: martin.hof@jh-inst.cas.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Hof
mesh_terms: D002412:Cations; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009943:Organophosphorus Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D002412:Cations; D008051:Lipid Bilayers; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D014867:Water
keywords: Cryo-TEM; DLS; Gene therapy; Non-viral DNA vector; Time-resolved fluorescence; Transfection