Headlines 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

Anne-Sophie Robbes, Jacques Jestin, Florian Meneau, Florent Dalmas, François Boué, and Fabrice Cousin,
Macromolecules 2022, 55, 15, 6876–6889.

We present a combined detailed monitoring of the respective evolutions of the structure of fillers by SAXS and conformation of polymeric chains by SANS under uniaxial stretching at various elongation ratios in a nanocomposite made of spherical magnetic nanoparticles of γFe₂O₃ dispersed in a matrix of polystyrene (PS) chains. We can make the structure of fillers in the nanocomposite before stretching very anisotropic, as we demonstrated in reference (Macromolecules,2011,44(22), 8858–8865), thanks to the appliance of a magnetic field during the nanocomposite processing that induces the formation of nanoparticle chains aligned along the direction of the field, either parallel or perpendicular to the subsequent stretching. This gives rise to very anisotropic mechanical properties, and the structure of fillers evolves very differently. In the parallel case, there is a rupture of the chains of nanoparticles into smaller subunits that progressively align completely in the stretching direction. In the perpendicular case, the chains first rotate, to eventually reorient along the stretching direction, gradually breaking themselves. Finally, at a very large elongation rate (λ = 6), the organization of nanoparticles in both cases converge toward a common structure made of small chains of nanoparticles completely oriented along the stretching. The chain conformation is directly obtained by SANS as we probed samples containing 25% PS_H/75% PS_D chains, taking benefit from the fact that the neutron scattering length density of PSD is similar to the one of γFe₂O₃. Strikingly, the deformation of the polymer chains is the same as in the reference PS matrix without fillers, whatever stretching is parallel and perpendicular to the chains of nanoparticles at λ = 3. The chains scattering exhibit the typical features of those of the former studies of relaxation during or after stretching on pure melts, accounting for the relatively slow deformation rate, the distance from T_g (15 °C) their average masses, and their large polydispersity.

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

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

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.

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

Eni Kume, Nicolas Martin, Peter Dunne, Patrick Baroni and Laurence Noirez
Molecules 2022, 27(22), 7829.

Mesoscopic shear elasticity has been revealed in ordinary liquids both experimentally by reinforcing the liquid/surface interfacial energy and theoretically by nonextensive models. The elastic effects are here examined in the frame of small molecules with strong electrostatic interactions such as room temperature ionic liquids [emim][Tf₂N] and nitrate solutions exhibiting paramagnetic properties. We first show that these charged fluids also exhibit a nonzero lowfrequency shear elasticity at the submillimeter scale, highlighting their resistance to shear stress. A neutron scattering study completes the dynamic mechanical analysis of the paramagnetic nitrate solution, evidencing that the magnetic properties do not induce the formation of a structure in the solution. We conclude that the elastic correlations contained in liquids usually considered as viscous away from any phase transition contribute in an effective way to collective effects under external stress or mechanical and magnetic fields.