Water-Peptide Site-Specific Interactions: A Structural Study on the Hydration of Glutathione

AbstractWater-peptide interactions play an important role in determining peptide structure and function. Nevertheless, a microscopic description of these interactions is still incomplete. In this study we have investigated at the atomic scale length the interaction between water and the tripeptide glutathione. The rationale behind this work, based on the combination between a neutron diffraction experiment and a computer simulation, is twofold. It extends previous studies on amino acids, addressing issues such as the perturbation of the water network brought by a larger biomolecule in solution. In addition, and more importantly, it seeks a possible link between the atomic length scale description of the glutathione-water interaction with the specific biological functionality of glutathione, an important intracellular antioxidant. Results indicate a rather weak hydrogen bond between the thiol (-SH) group of cysteine and its first neighbor water molecule. This -SH group serves as a proton donor, is responsible for the biological activity of glutathione, and it is involved in the formation of glutathione disulfide, the oxidized form of glutathione. Moreover, the hydration shell of the chemically identical carboxylate group on the glutamic acid residue and on the glycine residue shows an intriguing different spatial location of water molecules and coordination numbers around the two CO2− groups

The complex structure of Fomes fomentarius represents an architectural design for high-performance ultralightweight materials

We thank C. Li from the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany, for help during synchrotron measurements at the μSpot beamline at BESSY at the Helmholtz-Zentrum Berlin für Materialien und Energie in Berlin, Germany. We acknowledge the provision of facilities and technical support by Aalto University at the OtaNano Nanomicroscopy Center (Aalto-NMC). This work was supported by the Academy of Finland project 348628, the Jenny and Antti Wihuri Foundation (Centre for Young Synbio Scientists), and the Academy of Finland Center of Excellence Program (2022–2029) in Life-Inspired Hybrid Materials (LIBER) project number 346106, and by internal funding from the VTT Technical Research Center of Finland Ltd. We also acknowledge the Dutch Research Council (NWO, domain Applied and Engineering Sciences: MYCOAT project number 18425) and the Horizon 2020 programs of the European Union (FUNGAR; project 58132 and iNEXT-Discovery, project 871037) for NMR studies. Furthermore, the high-field NMR experiments were supported by uNMR-NL, the National Roadmap Large-Scale NMR Facility of the Netherlands (NWO grant 184.032.207), and the uNMR-NL grid (NWO grant 184.035.002).High strength, hardness, and fracture toughness are mechanical properties that are not commonly associated with the fleshy body of a fungus. Here, we show with detailed structural, chemical, and mechanical characterization that Fomes fomentarius is an exception, and its architectural design is a source of inspiration for an emerging class of ultralightweight high-performance materials. Our findings reveal that F. fomentarius is a functionally graded material with three distinct layers that undergo multiscale hierarchical self-assembly. Mycelium is the primary component in all layers. However, in each layer, mycelium exhibits a very distinct microstructure with unique preferential orientation, aspect ratio, density, and branch length. We also show that an extracellular matrix acts as a reinforcing adhesive that differs in each layer in terms of quantity, polymeric content, and interconnectivity. These findings demonstrate how the synergistic interplay of the aforementioned features results in distinct mechanical properties for each layer.Peer reviewe

Reflectometry Reveals Accumulation of Surfactant Impurities at Bare Oil/Water Interfaces

Bare interfaces between water and hydrophobic media like air or oil are of fundamental scientific interest and of great relevance for numerous applications. A number of observations involving water/hydrophobic interfaces have, however, eluded a consensus mechanistic interpretation so far. Recent theoretical studies ascribe these phenomena to an interfacial accumulation of charged surfactant impurities in water. In the present work, we show that identifying surfactant accumulation with X-ray reflectometry (XRR) or neutron reflectometry (NR) is challenging under conventional contrast configurations because interfacial surfactant layers are then hardly visible. On the other hand, both XRR and NR become more sensitive to surfactant accumulation when a suitable scattering length contrast is generated by using fluorinated oil. With this approach, significant interfacial accumulation of surfactant impurities at the bare oil/water interface is observed in experiments involving standard cleaning procedures. These results suggest that surfactant impurities may be a limiting factor for the investigation of fundamental phenomena involving water/hydrophobic interfaces

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers

Understanding the molecular mechanisms governing nanoparticle-membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse-grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di-stearoyl-phosphatidylcholine (DSPC) and anionic di-stearoyl-phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier. This can be overcome by increasing temperature, which promotes an irreversible AuNP incorporation into the lipid bilayer. NR experiments confirm the encapsulation of the AuNPs within the lipid bilayer at temperatures around 55 degrees C. In contrast, the AuNP adsorption is weak and impaired by heating for a DSPC-DSPG (3:1) lipid bilayer. These results demonstrate that both the lipid charge and the temperature play pivotal roles in AuNP-membrane interactions. Furthermore, NR experiments indicate that the (negative) DSPG lipids are associated with lipid extraction upon AuNP adsorption, which is confirmed by coarse-grained MD simulations as a lipid-crawling effect driving further AuNP aggregation. Overall, the obtained detailed molecular view of the interaction mechanisms sheds light on AuNP incorporation and membrane destabilization.Peer reviewe

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific data- bases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was euro2,558.91 and euro3,287.40 for subjects with micro- prolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after ini- tial treatment were euro798.13 and euro1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of euro3,201.15 compared to bromocriptine, based on a willingness-to-pay of euro40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic sur- gery was more cost-effective than cabergoline, with an ICER of euro44,846.64. Considering a willingness-to-pay of euro40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources

Extraction par solvant : étude d’une interface liquide/liquide contenant des ligants en associant des mesures de réflectivité de rayons X et de neutrons

In the frame of the nuclear waste reprocessing and various kinds of critical metals recycling methods, solvent extraction is one of the most used technological processes. The liquid interface between two immiscible fluids is considered as a region where many physical and chemical phenomena take place and can limit or promote the transfer of species between both fluids. The structure of these interfaces has to be known as a function of several thermodynamical parameters to be able to determine the associated energy landscape. X-ray and neutron reflectivity are suitable techniques to probe such kind of fluctuating and buried interfaces at the nanometer scale and at equilibrium. For this study, a new cell has been built and a specific data analysis procedure was established.We have focused our study on two different biphasic systems (water/dodecane) containing lanthanides salts and two different nonionic ligands or extractant molecules: DMDBTDMA and DMDOHEMA diamides. These ligands are known to have different behaviour in the lanthanides extraction process. Although the amphiphilic chemical structure of both diamides is well known, the structure of the liquid/liquid interface appears to be different as those expected for a classical surfactant molecule. This structure looks more complex, varies as a function of the ligand concentration in the organic phase (below the critical aggregation concentration) and as a function of the proton and salt concentration of the aqueous phase. A monolayer organization does not appear as the main interfacial structuration and a thicker organic layer with an excess of salt has to be considered.In the case of the DMDBTDMA, this thicker region (approximatively three or four times the length of the ligand) creates an interfacial region where oil and water molecules as well as some salts can mix in. The DMDOHEMA system shows a different structuration where we can roughly observe also a thick layer of the ligand (approximatively two times the length of the ligand) but located more within the oil phase and forming a barrier to the salt distribution. These different interfacial structures made of DMDBTDMA and DMDOHEMA could allow to explain the diffusive or kinetic regime of ion transfer observed respectively in similar systems by others authors.Dans le cadre du retraitement des déchets nucléaires et du recyclage de métaux critiques, l'extraction par solvant est l'une des technologies les plus utilisées. L'interface liquide entre deux fluides non miscibles est considérée comme une région où de multiples phénomènes physiques et chimiques sont à prendre en compte et peuvent limiter ou favoriser le transfert d'espèces entre les deux fluides. La structure de ces interfaces doit être connue en fonction de plusieurs paramètres thermodynamiques pour pouvoir déterminer le paysage énergétique associée. La réflectivité de neutrons et de rayons est un des outils appropriés pour sonder ce genre d'interfaces enfouies et fluctuantes à l'échelle nanométrique et à l'équilibre. Pour cette étude, une nouvelle cellule a été construite et un programme spécifique d'analyse de données a été élaboré.Nous avons également porté notre étude sur deux différents systèmes bi-phasiques (eau / dodécane) contenant des sels de lanthanides et deux différents ligands non ioniques (ou extractants) : une diamide de type DMDBTDMA et de type DMDOHEMA, ces deux extractants étant connus pour avoir des comportements différents dans un processus d'extraction de cations métalliques en phase organique. Bien que la structure amphiphile des deux diamides soit bien connue, la structure de l'interface liquide / liquide semble être différente de celle que l'on pourrait s'attendre avec des tensioactifs classiques. L'organisation de ces ligands à l'interface est en effet plus complexe, varie en fonction de leurs concentrations dans la phase organique (seules des concentrations inférieures à la concentration d'agrégation critique ont été étudiées) et en fonction de la concentration d'acide et de sel dans la phase aqueuse. Une organisation de type monocouche n'est pas l'organisation principale de ces systèmes à l'équilibre mais on observe plutôt une couche épaisse de ligands.Plus précisément, dans le cas de la DMDBTDMA, cette région plus épaisse (environ trois à quatre fois la longueur du ligand) crée une région interfaciale où les molécules d'huile et d'eau peuvent se mélanger ainsi que les sels. Le système DMDOHEMA, présente une structuration différente avec également une épaisse couche de ligand (environ deux fois la longueur du ligand) mais située plus à l'intérieur de la phase huileuse et distinct de la distribution des sels à l'interface. Ces différentes structures interfaciales de DMDBTDMA et DMDOHEMA peuvent permettre d'expliquer les différents régimes de transfert ionique qualifiés soit de diffusionnel ou de cinétique

Reflectometry Reveals Accumulation of Surfactant Impurities at Bare Oil/Water Interfaces

Bare interfaces between water and hydrophobic media like air or oil are of fundamental scientific interest and of great relevance for numerous applications. A number of observations involving water/hydrophobic interfaces have, however, eluded a consensus mechanistic interpretation so far. Recent theoretical studies ascribe these phenomena to an interfacial accumulation of charged surfactant impurities in water. In the present work, we show that identifying surfactant accumulation with X-ray reflectometry (XRR) or neutron reflectometry (NR) is challenging under conventional contrast configurations because interfacial surfactant layers are then hardly visible. On the other hand, both XRR and NR become more sensitive to surfactant accumulation when a suitable scattering length contrast is generated by using fluorinated oil. With this approach, significant interfacial accumulation of surfactant impurities at the bare oil/water interface is observed in experiments involving standard cleaning procedures. These results suggest that surfactant impurities may be a limiting factor for the investigation of fundamental phenomena involving water/hydrophobic interfaces

Neutrons and model membranes : Moving towards complexity

Cells, the basic units of living organisms, are well delineated and separated from the external environment by membranes. Capable of both enclosing the cellular constituents and allowing exchanges with the outside world, these membranes are only a few nanometers thick. All the membranes in a human body cover an area of a few hectares, but account for only a small part of our mass. To study the dynamics and function of these amazing objects, physicists first seek to understand their structure. This involves experiments on model systems, simpler and better controlled than real membranes, and can profit from a probe that is able to access different scales of size and time: thermal neutrons. Since the pioneering work in the seventies on cell membrane structure by neutron scattering, developments driven by constantly improving neutron instrumentation, coupled with development of measurement and analysis methods, have involved both the optimization of samples towards more biologically relevant model systems and include the use of more complex lipid mixtures up to natural extracts. This review does not have the ambition to address the large number of contributions from all the groups working in this area in research laboratories and neutron facilities. It gives an update on some studies in the field carried out mainly by the authors and collaborators

Biomimetic Approach for Sustainable Magnetite Nanoparticle Synthesis Using Polycations

Magnetotactic bacteria produce magnetite nanoparticles called magnetosomes at ambient conditions via a protein-stabilized transient amorphous precursor to obtain precise control over particle size and morphology. In a bioinspired approach, such biomineralization processes are emulated, mimicking proteins involved in magnetosome formation using the positively charged analog poly-L-arginine. While the additive is expensive, it remains elusive whether the change in magnetite formation mechanism arises solely from the polymer's cationic nature. This study uses different mass-produced and sustainably sourced polycations to induce the biomineralization-reminiscent formation of magnetite nanoparticles. These findings present how to achieve control over nanoparticle size (from 10 to 159 nm) and morphology (compact and sub-structured) as well as magnetic properties (superparamagnetic, stable-single-domain, vortex state) at ambient temperature and pressure using these additives. Furthermore, the formation of large nanoparticles with the addition of poly(diallyldimethylammonium chloride) (PDADMAC) at low alkalinity highlights how magnetotactic bacteria may produce magnetite nanoparticles under similar conditions. Confirming the polycations' ability to electrostatic stabilize amorphous ferrihydrite, it is anticipated that parametric in vitro studies on polymer properties will provide valuable insights into magnetite biomineralization and aid in rationally designing magnetic nanomaterials