The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide-dendrimer complexes with lipid membranes.
In this study, dendrimers have been purposed as an alternative approach for delivery of HIV peptides to dendritic cells. We have investigated the interaction of dendriplexes formed from polyanionic HIV peptide Nef and cationic carbosilane dendrimer (CBD) with model lipid membranes - large unilamellar vesicles (LUVs), Langmuir monolayers and supported lipid membranes (sBLMs) containing various molar ratio of zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000). In our experiments, the lipid membranes represented the model of the plasma membrane of the cell. PEGylated lipids were used in order to model glycocalyx which constitutes the outer leaflet of cellular membranes. The presence of PEGylated lipids resulted in an increase of the phase transition temperature of the lipid bilayer of LUVs, in a decrease of specific volume and adiabatic compressibility. Fluorescence anisotropy study suggests that PEGylated LUVs possessed higher lipid order and decreased fluidity when compared to zwitterionic DMPC vesicles. The interaction of dendriplexes with monolayers was accompanied by the formation of the aggregates as revealed by BAM experiments. This conclusion has been confirmed also by AFM imaging of sBLMs. We have demonstrated that dendriplexes interact with lipid membranes for all types of lipid composition. Moreover, the stronger interaction of cationic dendrimer/peptide complexes with lipid monolayers, vesicles and sBLMs was observed for membranes composed of zwitterionic lipids than for PEGylated lipid membranes. Increased concentration of PEGylated lipids made this interaction weaker.
Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska dolina, 842 48 Bratislava, Slovakia.
Sophie
S
Melikishvili
Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska dolina, 842 48 Bratislava, Slovakia; Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, 900 28 Ivanka pri Dunaji, Slovakia.
Alexandra
A
Poturnayova
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Maksim
M
Ionov
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Maria
M
Bryszewska
Institute of Nuclear and Physical Engineering, Slovak University of Technology, Ilkovicova 3, 812 19 Bratislava, Slovakia.
Tomáš
T
Vary
Institute of Nuclear and Physical Engineering, Slovak University of Technology, Ilkovicova 3, 812 19 Bratislava, Slovakia.
Julius
J
Cirak
Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Spanish HIV BioBank and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
María Ángeles
MÁ
Muñoz-Fernández
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá Henares, Spain.
Rafael
R
Gomez-Ramirez
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá Henares, Spain.
Francisco Javier
FJ
de la Mata
Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska dolina, 842 48 Bratislava, Slovakia. Electronic address: tibor.hianik@fmph.uniba.sk.
Tibor
T
Hianik
D050091:Dendrimers / Q000737:chemistry*; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012542:Scattering, Radiation; D013816:Thermodynamics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
D050091:Dendrimers; D008051:Lipid Bilayers; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D011092:Polyethylene Glycols
Carbosilane dendrimers; HIV-1 derived peptides; Lipid monolayers; Polyethylene glycol; Supported lipid films; Vesicles