3D Cryo-Electron Microscopy Reveals the Structure of a 3-Fluorenylmethyloxycarbonyl Zipper Motif Ensuring the Self-Assembly of Tripeptide Nanofibers.

Short peptide-based supramolecular hydrogels appeared as highly interesting materials for applications in many fields. The optimization of their properties relies mainly on the design of a suitable hydrogelator through an empirical trial-and-error strategy based on the synthesis of various types of peptides. This approach is in part due to the lack of prior structural knowledge of the molecular architecture of the various families of nanofibers.

Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb.

Mechanistic Insights into Hyaluronic Acid Induced Peptide Nanofiber Organization in Supramolecular Hydrogels.

Composite hydrogels composed of low-molecular-weight peptide self-assemblies and polysaccharides are gaining great interest as new types of biomaterials. Interactions between polysaccharides and peptide self-assemblies are well reported, but a molecular picture of their impact on the resulting material is still missing. Using the phosphorylated tripeptide precursor Fmoc-FFY (Fmoc, fluorenylmethyloxycarbonyl; F, phenylalanine; Y, tyrosine; , phosphate group), we investigated how hyaluronic acid (HA) influences the enzyme-assisted self-assembly of Fmoc-FFY generated in situ in the presence of alkaline phosphatase (AP).

Tear of lipid membranes by nanoparticles.

Health concerns associated with the advent of nanotechnologies have risen sharply when it was found that particles of nanoscopic dimensions reach the cell lumina. Plasma and organelle lipid membranes, which are exposed to both the incoming and the engulfed nanoparticles, are the primary targets of possible disruptions. However, reported adhesion, invagination and embedment of nanoparticles (NPs) do not compromise the membrane integrity, precluding direct bilayer damage as a mechanism for toxicity.

Gel-to-gel non-variant transition of an organogel caused by polymorphism from nanotubes to crystallites.

An amide based gelator forms gels in trans-decalin. Below concentrations of 1 wt% the gels melt at temperatures varying with concentration. Above a concentration of 1 wt%, upon heating, the gel transforms into an opaque gel at an invariant temperature, and melts at higher temperature.

Structure of Nanotubes Self-Assembled from a Monoamide Organogelator.

Some organic compounds are known to self-assemble into nanotubes in solutions, but the packing of the molecules into the walls of the tubes is known only in a very few cases. Herein, we study two compounds forming nanotubes in alkanes. They bear a secondary alkanamide chain linked to a benzoic acid propyl ester (HUB-3) or to a butyl ester (HUB-4).

Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering.

Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants in reverse cholesterol transport, and associated with reduced development of atherosclerosis. Here, we employed elastic incoherent neutron scattering (EINS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the average particle dynamics and protein backbone local mobility of physiologically competent discoidal and spherical HDL particles reconstituted with human apolipoprotein A-I (apoA-I).

Chain conformation: A key parameter driving clustering or dispersion in polyelectrolyte - Colloid systems.

The work presents the characterization of Pluronic F127 micellar solutions in presence of hyaluronic acid in semi-dilute regime. The effects of the nature and salt concentration are investigated by differential scanning calorimetry and small angle neutron scattering. Hyaluronic acid reduces the critical micellar temperature to the same extend as an increase of the ionic strength.

The fluctuating ribosome: thermal molecular dynamics characterized by neutron scattering.

Conformational changes associated with ribosome function have been identified by X-ray crystallography and cryo-electron microscopy. These methods, however, inform poorly on timescales. Neutron scattering is well adapted for direct measurements of thermal molecular dynamics, the 'lubricant' for the conformational fluctuations required for biological activity.

Neutrons describe ectoine effects on water H-bonding and hydration around a soluble protein and a cell membrane.

Understanding adaptation to extreme environments remains a challenge of high biotechnological potential for fundamental molecular biology. The cytosol of many microorganisms, isolated from saline environments, reversibly accumulates molar concentrations of the osmolyte ectoine to counterbalance fluctuating external salt concentrations. Although they have been studied extensively by thermodynamic and spectroscopic methods, direct experimental structural data have, so far, been lacking on ectoine-water-protein interactions.

SANS from Salt-Free Aqueous Solutions of Hydrophilic and Highly Charged Star-Branched Polyelectrolytes.

Scattering functions of sodium sulfonated polystyrene (NaPSS) star-branched polyelectrolytes with high sulfonation degrees were measured from their salt-free aqueous solutions, using the Small Angle Neutron Scattering (SANS) technique. Whatever the concentration , they display two maxima. The first, of abscissa ₁*, is related to a position order between star cores and scales as ₁* ∝ .

Hydration water mobility is enhanced around tau amyloid fibers.

The paired helical filaments (PHF) formed by the intrinsically disordered human protein tau are one of the pathological hallmarks of Alzheimer disease. PHF are fibers of amyloid nature that are composed of a rigid core and an unstructured fuzzy coat. The mechanisms of fiber formation, in particular the role that hydration water might play, remain poorly understood.

Dynamics of nanoscale polarization fluctuations in a uniaxial relaxor.

We have studied neutron diffuse scattering in a Sr(0.61)Ba(0.39)Nb(2)O(6) single crystal by neutron backscattering at sub-μeV energy resolution.

Proton diffusion in the hexafluorophosphoric acid clathrate hydrate.

The hexafluorophosphoric acid clathrate hydrate is known as a "super-protonic" conductor: its proton conductivity is of the order of 0.1 S/cm at ca. room temperature.

Evidence of dynamical constraints imposed by water organization around a bio-hydrophobic interface.

Molecular dynamics simulations and elastic neutron scattering experiments have been used to highlight how the structural organization of hydration water is able in some cases to locally constrain atomic movements at biologic interfaces. Using fully hydrated small peptides as models of protein interfaces, we show that the length of the side chains and the hydrophilic backbone have specific signatures. The dynamics of the side chain, which is part of biomolecules, have not only a crucial role in the whole flexibility as compared to the backbone, but also modify the values of transition temperatures.

A polymer surfactant corona dynamically replaces water in solvent-free protein liquids and ensures macromolecular flexibility and activity.

The observation of biological activity in solvent-free protein-polymer surfactant hybrids challenges the view of aqueous and nonaqueous solvents being unique promoters of protein dynamics linked to function. Here, we combine elastic incoherent neutron scattering and specific deuterium labeling to separately study protein and polymer motions in solvent-free hybrids. Myoglobin motions within the hybrid are found to closely resemble those of a hydrated protein, and motions of the polymer surfactant coating are similar to those of the hydration water, leading to the conclusion that the polymer surfactant coating plasticizes protein structures in a way similar to hydration water.

From chain collapse to new structures: spectroscopic properties of poly(3-thiophene acetic acid) upon binding by alkyl trimethylammonium bromide surfactants.

The binding of cationic surfactants with varying alkyl chain length to a regiorandom conjugated polyanion, poly(3-thiophene acetic acid) (PTAA), is studied in an aqueous buffer by using absorption and emission spectroscopies, photon correlation spectroscopy, isothermal titration calorimetry, and cryogenic transmission electron microscopy. We study the mixed solutions as a function of composition ratio R of surfactant molecules to monomer units molar concentrations, at low polymer concentration and in a very wide composition range (10(-6) < R < 10(2)) below the critical micellar concentration. Upon surfactant binding, the molecularly dispersed chains first collapse progressively and then form new structures as the mixed aggregates get enriched in surfactant.

Diffusion in solids studied by nuclear resonant X-ray and neutron scattering.

Nuclear resonant scattering of synchrotron radiation and quasielastic neutron scattering allow the measurement of frequencies, directions and lengths of jumps of diffusing atoms. Both methods have been successfully applied to diffusion in solids. Synergies and respective advantages of these two techniques as well as recent developments are discussed on the basis of an example: diffusion in intermetallic alloys.

Alanine metabolism in isolated human kidney tubules--Use of a mathematical model.

To gain insight into the fate of alanine nitrogen and carbon taken up by the human kidney under certain conditions, isolated human kidney cortex tubules were incubated in Krebs-Henseleit medium with L-alanine as substrate. The tubules metabolized alanine at high rates and in a dose-dependent manner. Most of the alanine nitrogen removed was recovered as ammonia and to a lesser extent as glutamate.

A simple model for alanine metabolism in isolated rat hepatocytes.

A simple model describing reactions of alanine metabolism in isolated hepatocytes from fasted rats is proposed and applied to radioactive data obtained in experiments in which L-[1-14C]-, L-[2-14C]-, L-[3-14C]-, and L-[U-14C]alanine as well as L-alanine plus NaH14CO3 were used as substrates in parallel. Measurements of the rates of incorporation of the label into glucose and CO2 and of accumulation of [1-14C]pyruvate, [1-14C]lactate, [1-14C]alanine and [1-14C]glutamate plus [1-14C]glutamine from the different substrates used allows to calculate flux of alanine carbon through the various metabolic steps taken into account in the model. The validity of this model is indicated by the agreement found between calculations and measurement of the 14CO2 released from [1-14C]alanine as well as between the values of flux through pyruvate carboxylase calculated in two different ways.

Vitamin K1 diffusion across the placental barrier in the gravid female rat.

The hemorrhagic disease of the newborn can be prevented by administration of vitamin K1. The modes of utilization of the vitamin need to be studied in the mother and child. An experimental pharmacokinetic study was conducted, using the gravid female rat.