The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide–dendrimer complexes with lipid membranes

Abstract

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-PEG). 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.

Visualizing Actin Packing and the Effects of Actin Attachment on Lipid Membrane Viscosity Using Molecular Rotors

“…We attributed this effect to the increased ratio of 18:1 Biotinyl Cap PE lipids that have bulkier headgroups than DOPC lipids. As previously reported, the presence of lipids with large headgroups ( e.g ., glycolipids, PEG-lipids) can increase the rigidity of model and live cell membranes. − …”

“…As previously reported, the presence of lipids with large headgroups ( e.g ., glycolipids, PEG-lipids) can increase the rigidity of model and live cell membranes. 54 − 56 …”

Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers

“…The scaffold of carbosilane dendrimers is made of very apolar C–C and Si–C bonds, being highly hydrophobic, while widely employed PAMAM, PPI, and polyester dendrimers contain a hydrophilic scaffold. The water solubility can be achieved by introducing ionic groups at the periphery, that is, cationic groups. , Moreover, the presence of ammonium functions at carbosilane dendrimer periphery has been useful to interact with anionic peptides − and also as nonviral vectors for gene therapy. , On the other hand, the hydrophobic framework of these dendrimers is also of relevance. Thus, cationic carbosilane dendrimers are able to cross the blood brain barrier , and smaller systems penetrate into the double strand of siRNA, establishing interactions through the hydrophobic moieties of both dendrimers and the RNA .…”

High-resolution ultrasonic spectroscopy

“…High sensitivity of compressibility β S to molecular organization and intermolecular interactions in the medium allows application of the HR-US technique in analysis of a broad range of molecular processes. This includes analysis of conformational transitions of polymers (Ochenduszko and Buckin, 2010;Perinelli et al, 2017;Van Durme et al, 2005;Wang et al, 2006), ligand binding (Jager et al, 2005;Kargerová and Pekař, 2014;Melikishvili et al, 2016), self-assembly and aggregation (Andreatta et al, 2005;Dalgleish et al, 2005;Klučáková and Věžníkova, 2016;Lehmann and Buckin, 2005), crystallisation and gelation (Lawrence et al, 2005;Lehmann et al, 2004;Smyth et al, 2001Smyth et al, , 2004Yuno-Ohta et al, 2016;Dalgleish et al, 2004), analysis of phase transitions and phase diagrams (Hickey et al, 2006(Hickey et al, , 2010, monitoring of chemical and biochemical reactions (Altas et al, 2016;Buckin and Altas, 2017;Resa and Buckin, 2011;Yuelong and Buckin, 2016), and others. Examples of these applications are outlined in Sect.…”