Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: A comparative study of experiments in silico and with cells

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca2+) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations.Fil: de Ménorval, Marie-Amélie. Centre National de la Recherche Scientifique; FranciaFil: Mir, Lluis M.. Centre National de la Recherche Scientifique; FranciaFil: Fernández, María Laura. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Computación. Laboratorio de Sistemas Complejos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reigada, Ramon. Universidad de Barcelona; Españ

Etude de la perméabilisation de la membrane plasmique et des membranes des organites cellulaires par des agents chimiques et physiques

It is possible to permeabilize the cellular plasma membrane by using chemical agents (as polyethylen glycols or diméthylsulfoxyde) or physical agents (as ulstrasounds or electric pulses). This permeabilization can be reversible or not, meaning that after the permeabilization, the membrane recovers its integrity and its hemi-permeable properties. These techniques can be used for the uptake of medicines or nucleic acids or to generate cellular fusions. A recent approach, the molecular dynamics, uses numerical simulations to predict the effects of permeabilizing agents at the molecular scale, allowed generating of new data to understand the molecular mechanisms that are not completely known yet.The pulses so called “classical” in electropermeabilization, from the range of the ten of milliseconds to the hundred of microseconds and with a field amplitude in the range of 100 kV/m, can only permeabilize the plasma membrane. However, more recently, shorter pulses, so called nanopulses (few nanosecondes) and with an higher field amplitude (in the range of 10 MV/m) have been used and allow to affect also cellular organelles membranes.This thesis is, in a first time, about the permeabilizing effects of a chemical gent (the diméthylsulfoxyde, DMSO) by comparing predictive models from molecular dynamics with experiments in vitro on cells. The numerical model predicts three regimes of action depending on the DMSO concentration. Used at low concentration, there is a plasma membrane deformation. The use of an intermediate concentration lead to membrane pores formation and higher DMSO concentrations resulted in membrane destruction. The experiments done in vitro on cells confirmed these results using the following of permeabilization markers. This study has been compared to permeabilization due to a physical agent (electric pulses).Secondly, it is about the development and the use of a new cell exposure device for nanopulses that permit to apply very high electric fields and to observe induced cellular effects simultaneously by microscopy.To finish, this device has been used with nanopulses to generate calcium peaks in mesenchymal stem cells that are presenting spontaneous calcium oscillations in correlation to their differentiation state.. These induced peaks are due to the release of the calcium stored in organelles and/or to plasma membrane permeabilization leading to a intramembrane calcium flux establishment. It is also possible to use microsecond pulses to generate calcium peaks in these cells. In this case, the calcium peaks are due to the plasma membrane permeabilization . By changing the amplitude of the applied electric fields and the presence or the absence of external calcium, it is possible to manipulate cytosolic calcium concentrations by mobilizing internal or external calcium. One feature of these new tools is to be triggered and stopped instantly without reminiscence, unlike chemical molecules permitting the production of calcium peaks. These tools could therefore lead to a better understanding of the involvement of calcium in mechanisms such as differentiation, migration or fertilization.Il est possible de perméabiliser la membrane plasmique des cellules par des agents chimiques (tels que les polyéthylènes glycols ou le diméthylsulfoxyde) ou par des agents physiques (tels que les ultrasons ou les impulsions électriques). Cette perméabilisation peut être réversible ou non, ce qui signifie qu’après la perméabilisation, la membrane retrouve son intégrité et ses propriétés d’hémi-perméabilité ou pas. Ces techniques peuvent être utilisées pour faire rentrer des médicaments ou des acides nucléiques dans les cellules ou pour générer des fusions cellulaires. Une approche récente, la dynamique moléculaire, utilise des simulations numériques pour prédire les effets des agents perméabilisants sur les membranes à l’échelle moléculaire, et permet d’apporter de nouvelles données pour comprendre les mécanismes moléculaires, encore peu connus à ce jour.Les impulsions dites « classiques » en électroperméabilisation, de l’ordre de la dizaine de millisecondes à la centaine de microsecondes et d’amplitude de champ de l’ordre de 100 kV/m, perméabilisent la membrane plasmique uniquement. Cependant, récemment, des impulsions plus courtes, dites impulsions nanoseconde (quelques nanosecondes) et de plus grande amplitude de champ (de l’ordre de 10 MV/m) ont été utilisées et permettent d’affecter également les membranes des organites cellulaires. Les travaux de cette thèse portent dans un premier temps sur les effets perméabilisants d’un agent chimique (le diméthylsulfoxyde, DMSO) en comparant les modèles prédictifs de la dynamique moléculaire avec des expériences in vitro sur des cellules. Le modèle numérique prédit trois régimes d’action en fonction de la concentration du DMSO. Utilisé à faible concentration, il y a déformation de la membrane plasmique. L’utilisation d’une concentration intermédiaire entraîne la formation de pores membranaires et les fortes concentrations de DMSO ont pour conséquence la destruction de la membrane. Les expériences in vitro faites sur des cellules ont confirmé ces résultats en suivant l’entrée de marqueurs de perméabilisation. Cette étude a été comparée avec la perméabilisation par un agent physique (les impulsions électriques). Dans un deuxième temps, ces travaux traitent du développement et de l’utilisation d’un nouveau dispositif d’exposition des cellules aux impulsions nanoseconde qui permet d’appliquer des champs électriques très élevés et d’observer par microscopie leurs au niveau cellulaire. Pour finir, ce dispositif a été utilisé avec des impulsions nanoseconde pour générer des pics calciques dans de cellules souches mésenchymateuses qui présentent des oscillations calciques spontanées liées à leur état de différenciation. Ces pics induits sont dus à la libération de calcium stocké dans les organites et/ou à la perméabilisation de la membrane plasmique permettant l’établissement d’un flux de calcium intramembranaire. Il est aussi possible d’utiliser des impulsions microseconde pour générer des pics calciques dans ces cellules. Dans ce cas, les pics calciques ne sont dus qu’à la perméabilisation de la membrane plasmique. En jouant sur l’amplitude des champs électriques appliqués et sur la présence ou l’absence de calcium externe, il est possible de manipuler les concentrations calciques cytosoliques en mobilisant le calcium interne ou externe. Une des particularités de ces nouveaux outils est de pouvoir être déclenchés et arrêtés instantanément, sans réminiscence, contrairement aux molécules chimiques permettant de produire des pics calciques. Ces outils pourraient donc permettre de mieux comprendre l’implication du calcium dans des mécanismes comme la différenciation, la migration ou la fécondation

Spectroscopic investigation of Titania-supported gold nanoparticles prepared by a modified deposition/precipitation method for the oxidation of CO

The spectroscopic characterization of a material is a fundamental tool for understanding the structure–activity correlation for catalytic purposes. Regarding supported nanoparticles, this perspective has acquired more relevance in recent years and several techniques have been employed. In this work diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), coupled with CO adsorption, was used to investigate a modified deposition/precipitation method (DP-UC) for the preparation of supported gold nanoparticles with very low metal loading (0.1–0.5 wt %). This promising synthetic route involves the use of urea as basic agent and NaBH4 as chemical reductant in contrast to the traditional high-temperature reduction step. The systematic IR spectroscopic study of the Au loading was combined with CO oxidation catalytic tests. The evaluation of the results was also supported by several other techniques, such as X-ray photoelectron spectroscopy, N2 physisorption, and transmission electron microscopy. Particular attention was given to the evaluation of the gold electronic state, surface dispersion, particle size, and the corresponding structure–activity relationship

Catalytic cracking of n-alkane naphtha: The impact of olefin addition and active sites differentiation

An extended dual kinetic model allows to fit the n-heptane cracking results working in a wide range of reaction conditions. The duality of the model is provided by the contribution of monomolecular and bimolecular cracking mechanisms. It takes into account the role played by the olefins formed on the global cracking or added within the feed. Furthermore by means of this model and the kinetic parameters obtained when cracking n-heptane on ZSM-5, it has been observed that, while some characterization techniques show a homogeneous zeolite surface from the point of view of the active sites, rigorous kinetic experiments point to the possibility that the reactant sees a heterogeneous surface with, at least, two groups of cracking active sites. Those differentiated active sites give different cracking rates and different activation energies for the process and, in the case of ZSM-5, could be assimilated to sites pointing to the 10R channels and sites pointing into the crossing of the 10R channels, mainly due to differences in kid site location and confinement effects. (C) 2015 Elsevier Inc. All rights reserved.Financial support by the Ministerio de Economia y Competitividad of Spain (MINECO) [Programa Estatal (Project MAT2012-31657) and Programa Consolider-Ingenio 2010 (Project MULTICAT)] is gratefully acknowledged.Corma Canós, A.; Mengual Cuquerella, J.; Miguel Dolz, PJ. (2015). Catalytic cracking of n-alkane naphtha: The impact of olefin addition and active sites differentiation. Journal of Catalysis. 330:520-532. https://doi.org/10.1016/j.jcat.2015.04.020S52053233

Multipore zeolites: synthesis and catalytic applications

[EN] In the last few years, important efforts have been made to synthesize so-called "multipore" zeolites, which contain channels of different dimensions within the same crystalline structure. This is a very attractive subject, since the presence of pores of different sizes would favor the preferential diffusion of reactants and products through those different channel systems, allowing unique catalytic activities for specific chemical processes. In this Review we describe the most attractive achievements in the rational synthesis of multipore zeolites, containing small to extra-large pores, and the improvements reported for relevant chemical processes when these multipore zeolites have been used as catalysts.Financial support by the Spanish Government-MINECO through “Severo Ochoa” (SEV 2012-0267), Consolider Ingenio 2010-Multicat, MAT2012-37160, MAT2012-31657 and Intramural-201480I015 is acknowledged.Moliner Marin, M.; Martínez, C.; Corma Canós, A. (2015). Multipore zeolites: synthesis and catalytic applications. Angewandte Chemie International Edition. 54(12):3560-3579. https://doi.org/10.1002/anie.201406344S35603579541

Paris (Région nord)

Basse de Ménorval Eliane. Paris (Région nord). In: Gallia préhistoire, tome 3, 1960. pp. 170-181

Ancienne circonscription de Paris

Basse de Ménorval Eliane. Ancienne circonscription de Paris. In: Gallia préhistoire, tome 9, fascicule 2, 1966. pp. 437-446

Paris (Région nord)

Basse de Ménorval Eliane. Paris (Région nord). In: Gallia préhistoire, tome 5, fascicule 1, 1962. pp. 173-185

Visite du site archéologique de Guiry-en-Vexin par le groupe parisien de l'A.F.D.U. (21 mai 1960)

Basse de Menorval Eliane. Visite du site archéologique de Guiry-en-Vexin par le groupe parisien de l'A.F.D.U. (21 mai 1960). In: Femmes Diplômées, n°35, 1960. pp. 24-30

Ancienne circonscription de Paris

Basse de Ménorval Eliane. Ancienne circonscription de Paris. In: Gallia préhistoire, tome 9, fascicule 2, 1966. pp. 437-446