Monitoring changes of paramagnetically-shifted 31P signals in phospholipid vesicles

Phospholipid vesicles are commonly used as biomimetics in the investigation of the interaction of various species with cell membranes. In this paper we present a 31P NMR investigation of a simple vesicle system using a paramagnetic shift reagent to probe the inner and outer layers of the lipid bilayer. Time-dependent changes in the 31P NMR signal are observed, which differ whether the paramagnetic species is inside or outside the vesicle, and on the choice of buffer solution used. An interpretation of these results is given in terms of the interaction of the paramagnetic shift reagent with the lipids

Structural rearrangement of model membranes by the peptide antibiotic NK-2

AbstractWe have developed a novel α-helical peptide antibiotic termed NK-2. It efficiently kills bacteria, but not human cells, by membrane destruction. This selectivity could be attributed to the different membrane lipid compositions of the target cells. To understand the mechanisms of selectivity and membrane destruction, we investigated the influence of NK-2 on the supramolecular aggregate structure, the phase transition behavior, the acyl chain fluidity, and the surface charges of phospholipids representative for the bacterial and the human cell cytoplasmic membranes. The cationic NK-2 binds to anionic phosphatidylglycerol liposomes, causing a thinning of the membrane and an increase in the phase transition temperature. However, this interaction is not solely of electrostatic but also of hydrophobic nature, indicated by an overcompensation of the Zeta potential. Whereas NK-2 has no effect on phosphatidylcholine liposomes, it enhances the fluidity of phosphatidylethanolamine acyl chains and lowers the phase transition enthalpy of the gel to liquid cristalline transition. The most dramatic effect, however, was observed for the lamellar/inverted hexagonal transition of phosphatidylethanolamine which was reduced by more than 10 °C. Thus, NK-2 promotes a negative membrane curvature which can lead to the collapse of the phosphatidylethanolamine-rich bacterial cytoplasmic membrane

Peptide interactions with bacterial lipopolysaccharides

Peptide and protein interactions with (lipo)polysaccharides are important in various biological contexts, including lipoprotein deposition at proteoglycan-covered endothelial surfaces in atherosclerosis, lectin functionality, and the interaction of antimicrobial and anti-inflammatory peptides and proteins with (lipo)polysaccharides. The latter of these areas, which is the topic of this review, has attracted considerable interest during the last few years, since antimicrobial peptides may offer novel therapeutic opportunities in an era of growing problems with antibiotic resistance, and persisting problems with both acute and chronic inflammation. In the present overview, physicochemical factors affecting peptide interactions with bacterial (lipo)polysaccharides are discussed, both in solution and at membrane interfaces. In doing so, an attempt is made to illustrate how physicochemical factors affect the antimicrobial and anti-endotoxic functionality of such peptides, and how knowledge on this can be translated into therapeutic opportunities, e.g., in sepsis. (C) 2013 Elsevier Ltd. All rights reserved

Characterization of permeability and morphological perturbations induced by nisin on phosphatidylcholine membranes.

Nisin is an antimicrobial peptide used as food preservative. To gain some insights into the hypothesis that its bactericidal activity is due to the perturbation of the lipid fraction of the bacterial plasmic membrane, we have investigated the effect of nisin on model phosphatidylcholine (PC) membranes. We show that nisin affects the PC membrane permeability, and this perturbation is modulated by the lipid composition. Nisin-induced leakage from PC vesicles is inhibited by the presence of cholesterol. This inhibition is associated with the formation of a liquid ordered phase in the presence of cholesterol, which most likely reduces nisin affinity for the membrane. Conversely, phosphatidylglycerol (PG), an anionic lipid, promotes nisin-induced leakage, and this promotion is associated with an increased affinity of the peptide for the bilayer because nisin is a cationic peptide. When the electrostatic interactions are encouraged by the presence of 70 mol% PG in PC, the inhibitory effect of cholesterol is not observed anymore. Nisin drastically modifies the morphology of the dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) multilamellar dispersion without causing a significant change in the gel-to-liquid crystalline phase transition of the lipid. The morphological changes are observed from (31)P and (2)H NMR and cryo-electron microscopy. From the NMR point of view, the interactions giving rise to a broad signal (quadrupolar interactions and chemical shift anisotropy for (2)H NMR and (31)P NMR, respectively) are partly averaged out in the presence of nisin. This phenomenon is interpreted by the formation of curved lipid planes that lead to the lipid lateral diffusion occurring in the intermediate motional regime. By cryo-electron microscopy, large amorphous aggregates containing small dense globular particles are observed for samples quenched from 25 and 50 degrees C. Long thread-like structures are also observed in the fluid phase. A structural description of DPPC/nisin complex, consistent with the experimental observation, is proposed. The presence of 30 mol% cholesterol in DPPC completely inhibits the morphological changes induced by nisin. Therefore, it is concluded that nisin can significantly perturb PC bilayers from both the permeability and the structural points of view, and these perturbations are modulated by the lipidic species in the bilayer

Hypertension portale compliquée d'hémorragie par rupture de varices œsophagiennes chez la femme enceinte

La prise en charge thérapeutique de l’hypertension portale en cours de grossesse compliquée d’hémorragie digestive par rupture de varices oesophagiennes fait appel actuellement aux moyens endoscopiques : la sclérose et la ligature qui sont efficaces, tolérables et sans danger ni pour la mère ni pour la foetus. Nous rapportons trois cas traités avec succès par sclérothérapie : deux patientes ont été sclérosées en urgence après saignement digestif pendant leur grossesse, pour la 3ème patiente, la sclérothérapie a été démarrée avant la grossesse et les séances ont été poursuivies durant la grossesse sans aucun danger ni pour la mère ni pour le foetus

Iron(II) Complexes of 2,6-Di[4-(ethylcarboxy)pyrazol-1-yl]pyridine with Reversible Guest-Modulated Spin-Crossover Behavior

Tres solvatomorfos del complejo de hierro(II) de 2,6-di[4-(etilcarboxi)pirazol-1-il]piridina (bpCOOEt2p) de fórmulas [Fe(bpCOOEt2p)2](ClO4)2·1.5MeNO2 (1) , [Fe(bpCOOEt2p)2](ClO4)2·MeNO2 (2) y [Fe(bpCOOEt2p)2](ClO4)2·2MeNO2 (3) han sido preparados y caracterizados. Muestran interesantes propiedades de cruce de espín (SCO) que van desde transiciones de espín térmico parciales a completas y un efecto de captura de estado de espín excitado inducido por la luz (LIESST). En solvatomorph 2, se forma una estructura robusta con canales que permiten la entrada o eliminación de moléculas de solvente por difusión de vapor sin perder la cristalinidad. Por lo tanto, las muestras intercambiadas con disolvente [Fe(bpCOOEt2p)2](ClO4)2·MeNO2 (2·MeNO2), [Fe(bpCOOEt2p)2(ClO4)2·MeCN (2·MeCN), [Fe(bpCOOEt2p)2] (ClO4)2·0.5Me2CO (2·Me2CO), y [Fe(bpCOOEt2p)2](ClO4)2· MeCOOH (2·MeCOOH) fueron preparados por difusión de vapor de los solventes en un cristal del compuesto previamente calentado a 400 K en un monocristal a monocristal (SCSC) moda. Curiosamente, esto provoca un cambio de estado de espín con una estabilización del estado de espín bajo en 2·Me2CO y el estado de espín alto en 2·MeCN. Por lo tanto, las propiedades de SCO de 2 se pueden ajustar de forma reversible mediante la exposición a diferentes disolventes.03866