Novel Poly(Vinylidene Fluoride)/Montmorillonite Polymer Inclusion Membrane: Application to Cr(VI) Extraction from Polluted Water

Novel hybrid polymer inclusion membranes (PIMs) based on poly(vinylidene fluoride) (PVDF) (polymer matrix) and Aliquat 336 (ion carrier) and containing native sodium (Cloisite Na+ (CNa)) and organo-modified (Cloisite 30B (C30B)) Montmorillonites were elaborated and tested for the removal of toxic Cr(VI) ions from the aqueous solution. The influence of the nanoclay incorporation on the physicochemical properties of PVDF-based PIMs was studied and the resulting membrane transport properties of the Cr(VI) ions were investigated in detail. The water contact angle measurements reveal that the incorporation of the CNa nanofiller affects the membrane wettability as less hydrophilic surface is obtained in this case—~47° in the presence of CNa as compared with ~15° for PIMs with C30B. The membrane rigidity is found to be dependent on the type and size of the used Montmorillonite. The increase of Young’s modulus is higher when CNa is incorporated in comparison with C30B. The stiffness of the PIM is strongly increased with CNa amount (four times higher with 30 wt %) which is not the case for C30B (only 1.5 times). Higher Cr(VI) permeation flux is obtained for PIMs containing CNa (~2.7 µmol/(m2·s)) owing to their porous structure as compared with membranes loaded with C30B and those without filler (~2 µmol/(m2·s) in both cases). The PIM with 20 wt % of native sodium Montmorillonite revealed satisfactory stability during five cycles of the Cr(VI) transport due to the high membrane rigidity and hydrophobicity. Much lower macromolecular chain mobility in this case allows limiting the carrier loss, thus increasing the membrane stability. On the contrary, a deterioration of the transport performance is recorded for the membrane filled with C30B and that without filler. The obtained results showed the possibility to extend the PIM lifetime through the incorporation of nanoparticles that diminish the carrier loss (Aliquat 336) from the membrane into the aqueous phase by limiting its mobility within the membrane by tortuosity effect and membrane stiffening without losing its permselective properties.

Flavonoid-Coated Gold Nanoparticles as Efficient Antibiotics against Gram-Negative Bacteria—Evidence from In Silico-Supported In Vitro Studies

Flavonoids are a class of bioactive plant-derived natural products that exhibit a broad range of biological activities, including antibacterial ones. Their inhibitory activity toward Gram-positive bacterial was found to be superior to that against Gram-negative ones. In the present study, a number of flavonoid-coated gold nanoparticles (GNPs) were designed to enhance the antibacterial effects of chrysin, kaempferol, and quercetin against a number of Gram-negative bacteria. The prepared GNPs were able to conjugate to these three flavonoids with conjugation efficiency ranging from 41% to 80%. Additionally, they were able to exert an enhanced antibacterial activity in comparison with the free flavonoids and the unconjugated GNPs. Quercetin-coated GNPs were the most active nano-conjugates and were able to penetrate the cell wall of E. coli. A number of in silico experiments were carried out to explain the conjugation efficiency and the antibacterial mechanisms of these flavonoids as follows: (i) these flavonoids can efficiently bind to the glutathione linker on the surface of GNPs via H-bonding; (ii) these flavonoids, particularly quercetin, were able to increase the bacterial membrane rigidity, and hence decrease its functionality; (iii) these flavonoids can inhibit E. coli’s DNA gyrase (Gyr-B) with IC50 values ranging from 0.9 to 3.9 µM. In conclusion, these bioactive flavonoid-based GNPs are considered to be very promising antibiotic candidates for further development and evaluation.

Stiffness of fluid and gel phase lipid nanovesicles: weighting the contributions of membrane bending modulus and luminal pressurization

The mechanical properties of biogenic membranous compartments are thought to be relevant in numerous biological processes; however, their quantitative measurement remains challenging for most of the already available Force Spectroscopy (FS)-based techniques. In particular, the debate on the mechanics of lipid nanovesicles and on the interpretation of their mechanical response to an applied force is still open. This is mostly due to the current lack of a unified model being able to describe the mechanical response of gel and fluid phase lipid vesicles and to disentangle the contributions of membrane rigidity and luminal pressure. In this framework, we herein propose a simple model in which the contributions of membrane rigidity and luminal pressure to the overall vesicle stiffness are described as a series of springs; this approach allows estimating the two contributions for both gel and fluid phase liposomes. Atomic Force Microscopy-based FS (AFM-FS), performed on both vesicles and Supported Lipid Bilayers (SLBs), is exploited for obtaining all the parameters involved in the model. Moreover, the use of coarse-grained full-scale molecular dynamics simulations allowed for better understanding the differences in the mechanical responses of gel and fluid phase bilayers and supported the experimental findings. Results suggest that the pressure contribution is similar among all the probed vesicle types; however, it plays a dominant role in the mechanical response of lipid nanovesicles presenting a fluid phase membrane, while its contribution becomes comparable to the one of membrane rigidity in nanovesicles with a gel phase lipid membrane. The herein presented results offer a simple way to quantify two of the most important parameters in vesicular nanomechanics, and as such represent a first step towards a currently unavailable, unified model for the mechanical response of gel and fluid phase lipid nanovesicles.

Membrane Environment Modulates Ligand-Binding Propensity of P2Y12 Receptor

The binding of natural ligands and synthetic drugs to the P2Y12 receptor is of great interest because of its crucial role in platelets activation and the therapy of arterial thrombosis. Up to now, all computational studies of P2Y12 concentrated on the available crystal structures, while the role of intrinsic protein dynamics and the membrane environment in the functioning of P2Y12 was not clear. In this work, we performed all-atom molecular dynamics simulations of the full-length P2Y12 receptor in three different membrane environments and in two possible conformations derived from available crystal structures. The binding of ticagrelor, its two major metabolites, adenosine diphosphate (ADP) and 2-Methylthioadenosine diphosphate (2MeS-ADP) as agonist, and ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate (AZD1283)as antagonist were assessed systematically by means of ensemble docking. It is shown that the binding of all ligands becomes systematically stronger with the increase of the membrane rigidity. Binding of all ligands to the agonist-bound-like conformations is systematically stronger in comparison to antagonist-bound-likes ones. This is dramatically opposite to the results obtained for static crystal structures. Our results show that accounting for internal protein dynamics, strongly modulated by its lipid environment, is crucial for correct assessment of the ligand binding to P2Y12.

Quercetin Induces Lipid Domain-Dependent Permeability

In this work, we present our results on quercetin interaction with distinct model membranes exploring the importance of lipid phases, ld, ld/lo and ld+lo+so, to the action of this flavonoid in bilayers and possibly contributing to clarifying some controversial aspects related to quercetin multiple activities. We found out that quercetin is able to increase membrane permeability in a manner dependent on the presence and characteristics of lipid domains. In the presence of sphingomyelin, we found the greatest increase in mean membrane permeability (at least 10 times higher than the other lipid compositions). We also observed the presence of micrometric domains whose shape and size were disturbed by the action of quercetin. The presence of cholesterol increased membrane rigidity. This effect was enhanced with the presence of quercetin, but for chol-sphingomyelin combination, the bilayers became more flaccid at low quercetin/lipid proportions (< 1/5) and moderately rigid at proportions of the 1/1 order. The affinity parameters were higher for the most homogeneous systems and with larger areas and extensions of disordered liquid phase than for those systems of higher heterogeneity.

Quercetin Induces Lipid Domain-Dependent Permeability

In this work, we present our results on quercetin interaction with distinct model membranes exploring the importance of lipid phases, ld, ld/lo and ld+lo+so, to the action of this flavonoid in bilayers and possibly contributing to clarifying some controversial aspects related to quercetin multiple activities. We found out that quercetin is able to increase membrane permeability in a manner dependent on the presence and characteristics of lipid domains. In the presence of sphingomyelin, we found the greatest increase in mean membrane permeability (at least 10 times higher than the other lipid compositions). We also observed the presence of micrometric domains whose shape and size were disturbed by the action of quercetin. The presence of cholesterol increased membrane rigidity. This effect was enhanced with the presence of quercetin, but for chol-sphingomyelin combination, the bilayers became more flaccid at low quercetin/lipid proportions (< 1/5) and moderately rigid at proportions of the 1/1 order. The affinity parameters were higher for the most homogeneous systems and with larger areas and extensions of disordered liquid phase than for those systems of higher heterogeneity.

Quercetin Induces Lipid Domain-Dependent Permeability

In this work, we present our results on quercetin interaction with distinct model membranes exploring the importance of lipid phases, ld, ld/lo and ld+lo+so, to the action of this flavonoid in bilayers and possibly contributing to clarifying some controversial aspects related to quercetin multiple activities. We found out that quercetin is able to increase membrane permeability in a manner dependent on the presence and characteristics of lipid domains. In the presence of sphingomyelin, we found the greatest increase in mean membrane permeability (at least 10 times higher than the other lipid compositions). We also observed the presence of micrometric domains whose shape and size were disturbed by the action of quercetin. The presence of cholesterol increased membrane rigidity. This effect was enhanced with the presence of quercetin, but for chol-sphingomyelin combination, the bilayers became more flaccid at low quercetin/lipid proportions (< 1/5) and moderately rigid at proportions of the 1/1 order. The affinity parameters were higher for the most homogeneous systems and with larger areas and extensions of disordered liquid phase than for those systems of higher heterogeneity.

О молекулярной природе различий в реакции сенсорных нейронов и фибробластов на уабаин

Atomic force microscopy was used to study under physiologically adequate conditions the effect of ouabain on the mechanical characteristics of sensory neurons and fibroblasts of 10–12-day old chick embryos. Fibroblasts express only the α1-isoform of Na,K-ATPase, and sensory neurons the α1- and α3-isoforms. It was found that the action of ouabain at a concentration corresponding to the endogenous value leads to an increase in the membrane rigidity of sensory neurons, which is apparently due to the activation of the transducer function of Na,K-ATPase, rather than the pumping function. The endogenous concentration of ouabain did not change the mechanical characteristics of fibroblasts. The results obtained suggest that endogenous ouabain modulates the transducer function of the α3-isoform of Na,K-ATPase of the sensory neuron membrane. Thus, the method of atomic force microscopy allows a comparative study of intracellular signaling cascades in living cells.