Magnetically controlled insertion of magnetic nanoparticles into membrane model.

Polysaccharide-coated magnetic nanoparticles (MNPs) have been reported to show potential applications in many biomedical fields. In this report, we have studied the interactions between magnetite (Fe3O4) MNPs functionalized with polysaccharides (diethylamino-ethyl dextran, DEAE-D or chitosan, CHI) with different membranes models by Langmuir isotherms, incorporation experiments, and brewster angle microscopy (BAM). In this report, zwitterionic 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE) and anionic 1,2-distearoyl-sn-glycerol-3-phosphate (DSPA) phospholipid, were used to form membrane models. Incorporation experiments (π-t) as well as the compression isotherms demonstrate positive interactions between MNPs and DSPE or DSPA monolayers. The study assessed the impact of varying initial surface pressure on a preformed phospholipid monolayer to determine the maximum insertion pressure (MIP) and synergy. Our findings indicate that the primary driving force of the coated MNPs incorporation into the monolayer predominantly stems from electrostatic interaction. The drop in the subphase pH from 6.0 to 4.0 led to an enhancement of the MIP value for DSPA phospholipid monolayer. On the other hand, for DSPE, the drop in the pH does not affect the MIP values. Besides, the presence of a magnetic field induces an enhancement of the insertion process of the MNPs into DSPA preformed monolayer, demonstrating that a previous interaction between MNPs and phospholipid preformed monolayer needs to take place to enhance the incorporation process. This work opens novel perspectives for the research of the influence of magnetic fields on the incorporation of MNPs into model membranes.

Interaction of a Polyarginine Peptide with Membranes of Different Mechanical Properties.

The membrane translocation efficiency of cell penetrating peptides (CPPs) has been largely studied, and poly-arginines have been highlighted as particularly active CPPs, especially upon negatively charged membranes. Here we inquire about the influence of membrane mechanical properties in poly-arginine adsorption, penetration and translocation, as well as the subsequent effect on the host membrane. For this, we selected anionic membranes exhibiting different rigidity and fluidity, and exposed them to the nona-arginine KR9C. Three different membrane compositions were investigated, all of them having 50% of the anionic lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG), thus, ensuring a high affinity of the peptide for membrane surfaces. The remaining 50% was a saturated PC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC), an unsaturated PC (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) or a mixture of DOPC with cholesterol. Peptide-membrane interactions were studied using four complementary models for membranes: Langmuir monolayers, Large Unilamellar Vesicles, Black Lipid Membranes and Giant Unilamellar Vesicles. The patterns of interaction of KR9C varied within the different membrane compositions. The peptide strongly adsorbed on membranes with cholesterol, but did not incorporate or translocate them. KR9C stabilized phase segregation in DPPC/DOPG films and promoted vesicle rupture. DOPC/DOPG appeared like the better host for peptide translocation: KR9C adsorbed, inserted and translocated these membranes without breaking them, despite softening was observed.

Destabilizing effect of perfluorodecanoic acid on simple membrane models.

Perfluoroalkyl acids (PFA) are amphiphilic surfactants widely used in industry with several commercial applications. An important feature of these compounds is their non-biodegradability and their tendency to bio-accumulate in the environment, which has led to these compounds being considered among the most persistent pollutants worldwide. Many studies have provided evidence of their toxic effect on humans and wildlife. For this reason, more and more efforts have been made to better understand the effect of these compounds on living organisms. The aim of the present study is to understand how the electrostatic interactions and film compactness of biological membrane models modulate their interaction with PFA, more specifically with perfluorodecanoic acid (PFD). Langmuir isotherms and Brewster angle microscopy (BAM) are used to evaluate the effect of PFD on lipid membrane models (air/water monolayers and vesicles), analyzing the behavior of PFD : lipid mixtures. The lipids used in this study are distearoyl phosphatidic acid (DSPA), dilauroyl phosphatidic acid (DLPA) and distearoyl phosphatidylethanolamine (DSPE). PFD induces an increase in the mean molecular area per lipid in monolayers, mainly at lower surface pressures. BAM images demonstrate that PFD mixes with DLPA, inducing a decrease in gray level, while it forms a non-miscible mixture with DSPA, segregating PFD domains. Insertion studies of PFD within monolayers and dynamic light scattering experiments demonstrate that PFD can penetrate into monolayers and bilayers above 30 mN m-1, which is the lateral pressure value accepted for a cellular bilayer.

Mechanical Stability of Lipid Membranes Decorated with Dextran Sulfate.

Lipid vesicles decorated with polysaccharides have been proposed as vehicles for drug delivery because the polymers confer to the vesicles an enhanced stability, increasing the probability of the drug for reaching the target cell. Here, we first test the affinity of dextran sulfate (DS) for two different vesicle composition, and afterward, we study the effect of DS on the liposome mechanical properties. We found that DS binds to both tested membrane compositions. The interaction of DS with the anionic membranes studied here is mediated by the metal ions present in the aqueous solution (Na+ and Ca2+), being higher in the presence of Ca2+. Binding occurs preferentially in regions of closely packed lipids. Strikingly, DS did not affect the stability against detergent and the membrane rigidity of none of the vesicles. Thus, the proposed stability increase induced by this kind of polymers in drug delivery systems is not related with a modulation of the membrane thermodynamic properties but to other biochemical factors.

Interaction of dextran derivatives with lipid monolayers and the consequential modulation of the film properties.

Polysaccharides have been associated with various biological functions through their binding to membranes, but their specific role is still under debate. The aim of this work was to study the interaction of cationic and anionic polysaccharides with anionic and zwitterionic monolayers, at different subphase compositions, thus analyzing the influence of electrostatics on the interaction. The consequent effect of the polymer-lipid binding on the film properties was studied, with special interest in monolayer dynamics. The results indicate that electrostatic interactions play an important role in polymer-membrane affinity, and that the polymers formed a sub-layer, which increased the shear viscosity of the interface. The interacting polymer, even when it did not penetrate the lipid film, induced a polymer-like behavior of the monolayer regarding its dynamics: the whole film (polymer+lipid) became very viscous. As a consequence, the dynamic of the membrane was affected, thus inducing changes in the film topography, although the energetics for phase transition and the stability of each phase were modified slightly or not at all.