Laboratoire Léon Brillouin

UMR12 CEA-CNRS, Bât. 563 CEA Saclay

91191 Gif sur Yvette Cedex, France

+33-169085241 llb-sec@cea.fr

BD diffusons les neutrons

Faits marquants scientifiques 2023

02 mai 2023

Céline JAUDOIN, Isabelle GRILLO, Fabrice COUSIN, Maria GEHRKE, Malika OULDALI, Ana-Andreea ARTENI, Luc PICTON, Christophe RIHOUEY, Fanny SIMELIERE, Amélie BOCHOT, Florence AGNELY

Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid–polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.5% HA) at high liposome concentration (80 mM lipids). The objective was to elucidate the influence of liposome surface (neutral, cationic, anionic or anionic PEGylated), drug encapsulation and HA concentration in a buffer mimicking biological fluids (37 °C). First, liposomes were characterized by SANS, cryo-electron microscopy, and dynamic light scattering and HA by SANS, size exclusion chromatography, and rheology. Secondly, HA-liposome mixtures were studied by SANS. In HA, liposomes kept their integrity. Anionic and PEGylated liposomes were in close contact within dense clusters with an amorphous organization. The center-to-center distance between liposomes corresponded to twice their diameter. A depletion mechanism could explain these findings. Encapsulation of a corticoid did not modify this organization. Cationic liposomes formed less dense aggregates and were better dispersed due to their complexation with HA. Liposome surface governed the interactions and microstructure of these hybrid systems.

https://doi.org/10.1016/j.jcis.2022.07.146

 

23 mai 2023

Özge Azeri, Dennis Schönfeld, Bin Dai, Uwe Keiderling, Laurence Noirez and Michael Gradzielski

Block copolymers synthesized via Atom Transfer Radical Polymerization from alkyl acrylate and t-butyl acrylate and the subsequent hydrolysis of the t-butyl acrylate to acrylic acid were systematically varied with respect to their hydrophobic part by the variation in the alkyl chain length and the degree of polymerisation in this block. Depending on the architecture of the hydrophobic part, they had a more or less pronounced tendency to form copolymer micelles in an aqueous solution. They were employed for the preparation of IPECs by mixing the copolymer aggregates with the polycations polydiallyldimethylammonium chloride (PDADMAC) or q-chit. The IPEC structure as a function of the composition was investigated by Static Light and Small Angle Neutron Scattering. For weakly-associated block copolymers (short alkyl chain), complexation with polycation led to the formation of globular complexes, while already existing micelles (long alkyl chain) grew further in mass. In general, aggregates became larger upon the addition of further polycation, but this growth was much more pronounced for PDADMAC compared to q-chit, thereby leading to the formation of clusters of aggregates. Accordingly, the structure of such IPECs with a hydrophobic block depended largely on the type of complexing polyelectrolyte, which allowed for controlling the structural organisation via the molecular architecture of the two oppositely charged polyelectrolytes.

https://doi.org/10.3390/polym15092204

02 mai 2023

Céline JAUDOIN, Isabelle GRILLO, Fabrice COUSIN, Maria GEHRKE, Malika OULDALI, Ana-Andreea ARTENI, Luc PICTON, Christophe RIHOUEY, Fanny SIMELIERE, Amélie BOCHOT, Florence AGNELY

Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid–polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.5% HA) at high liposome concentration (80 mM lipids). The objective was to elucidate the influence of liposome surface (neutral, cationic, anionic or anionic PEGylated), drug encapsulation and HA concentration in a buffer mimicking biological fluids (37 °C). First, liposomes were characterized by SANS, cryo-electron microscopy, and dynamic light scattering and HA by SANS, size exclusion chromatography, and rheology. Secondly, HA-liposome mixtures were studied by SANS. In HA, liposomes kept their integrity. Anionic and PEGylated liposomes were in close contact within dense clusters with an amorphous organization. The center-to-center distance between liposomes corresponded to twice their diameter. A depletion mechanism could explain these findings. Encapsulation of a corticoid did not modify this organization. Cationic liposomes formed less dense aggregates and were better dispersed due to their complexation with HA. Liposome surface governed the interactions and microstructure of these hybrid systems.

https://doi.org/10.1016/j.jcis.2022.07.146

 

14 mars 2023

Michal Swierczewski,  Fabrice Cousin,  Ewa Banach,  Arnulf Rosspeintner,  Latevi Max Lawson Daku,  Abolfazl Ziarati,  Rania Kazan,  Gunnar Jeschke,  Raymond Azoulay,  Lay-Theng Lee,  Thomas Bürgi

A bidentate chiral dithiol (diBINAS) is utilised to bridge Au25 nanoclusters to form oligomers. Separation by size allows the isolation of fractions that are stable thanks to the bidentate nature of the linker. The structure of the products is elucidated by small-angle X-ray scattering and calculated using density functional theory. Additional structural details are studied by diffusion-ordered nuclear magnetic resonance spectroscopy, transmission electron microscopy and matrix-assisted laser desorption/ionization time of flight mass spectrometry. Significant changes in the optical properties are analysed by UV-Vis and fluorescence spectroscopies, with the latter demonstrating a strong emission enhancement. Furthermore, the emergent chiral characteristics are studied by circular dichroism. Due to the geometry constraints of the nanocluster assemblies, diBINAS can be regarded as a templating molecule, taking a step towards the directed self-assembly of metal clusters.

https://doi.org/10.1002/anie.202215746

 

27 janvier 2023

Sophie Combet, Françoise Bonneté, Stéphanie Finet, Alexandre Pozza, Christelle Saade, Anne Martel, Alexandros Koutsioubas, Jean-Jacques Lacapère, Biochimie (2022) in press.
 

The translocator protein (TSPO) is a ubiquitous transmembrane protein of great pharmacological interest thanks to its high affinity to many drug ligands. The only high-resolution 3D-structure known for mammalian TSPO was obtained by NMR for the mouse mTSPO in DPC detergent only in presence of the high-affinity PK 11195 ligand. An atomic structure of free-ligand mTSPO is still missing to better understand the interaction of ligands with mTSPO and their effects on the protein conformation.

19 février 2023

Florian Turbant, Jehan Waeytens, Camille Campidelli, Marianne Bombled, Denis Martinez, Axelle Grélard, Birgit Habenstein, Vincent Raussens, Marisela Velez, Frank Wien, Véronique Arluison

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.

https://doi.org/10.3390/ijms23158739

27 janvier 2023

Sophie Combet, Françoise Bonneté, Stéphanie Finet, Alexandre Pozza, Christelle Saade, Anne Martel, Alexandros Koutsioubas, Jean-Jacques Lacapère, Biochimie (2022) in press.
 

The translocator protein (TSPO) is a ubiquitous transmembrane protein of great pharmacological interest thanks to its high affinity to many drug ligands. The only high-resolution 3D-structure known for mammalian TSPO was obtained by NMR for the mouse mTSPO in DPC detergent only in presence of the high-affinity PK 11195 ligand. An atomic structure of free-ligand mTSPO is still missing to better understand the interaction of ligands with mTSPO and their effects on the protein conformation.

20 avril 2023

Les clusters métalliques dans la gamme de 10-300 atomes (diamètre 1 à 2 nm) forment une classe spécifique de matériaux dont les propriétés dépendent fortement de leur taille en raison de la discrétisation de leurs niveaux d’énergie. Cette spécificité leur apporte des propriétés originales pouvant ouvrir de multiples applications dans des dispositifs électroniques, optiques ou catalytiques. Ces applications exigent cependant d’exploiter la réponse collective d'assemblages, avec une organisation contrôlée de ces clusters, dont le plus prometteur, bien que difficile à réaliser, requiert la formation de films minces organisés à grande échelle.

L'équipe du LLB en collaboration avec le Département de Chimie-Physique de Genève, a ainsi étudié la formation et le dépôt de films minces de nanoclusters d’or stabilisés par un thiolate (Au38-R), par la technique de Langmuir-Blodgett (LB), afin d'obtenir des films bien organisés à grande échelle. Les propriétés structurales des films déposés sont caractérisées par la réflectivité de rayons-X, et les propriétés mécaniques sont sondées quantitativement par une technique originale : la microscopie à force atomique bimodale, à double cantilevers de rigidité contrastée.

02 mai 2023

Céline JAUDOIN, Isabelle GRILLO, Fabrice COUSIN, Maria GEHRKE, Malika OULDALI, Ana-Andreea ARTENI, Luc PICTON, Christophe RIHOUEY, Fanny SIMELIERE, Amélie BOCHOT, Florence AGNELY

Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid–polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.5% HA) at high liposome concentration (80 mM lipids). The objective was to elucidate the influence of liposome surface (neutral, cationic, anionic or anionic PEGylated), drug encapsulation and HA concentration in a buffer mimicking biological fluids (37 °C). First, liposomes were characterized by SANS, cryo-electron microscopy, and dynamic light scattering and HA by SANS, size exclusion chromatography, and rheology. Secondly, HA-liposome mixtures were studied by SANS. In HA, liposomes kept their integrity. Anionic and PEGylated liposomes were in close contact within dense clusters with an amorphous organization. The center-to-center distance between liposomes corresponded to twice their diameter. A depletion mechanism could explain these findings. Encapsulation of a corticoid did not modify this organization. Cationic liposomes formed less dense aggregates and were better dispersed due to their complexation with HA. Liposome surface governed the interactions and microstructure of these hybrid systems.

https://doi.org/10.1016/j.jcis.2022.07.146

 


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