Intravenous iron-carbohydrate complexes are widely used nanomedicines for the treatment of iron deficiency anaemia, particularly in patients with conditions like chronic kidney disease, heart failure and inflammatory diseases. Despite the abundance of physicochemical characterization and clinical studies for these products, a clear evidence-based correlation between physicochemical properties and clinical outcome of iron-carbohydrate complexes is yet to be established. There is, nonetheless, clear evidence that the nano-bio interface determines the bio-response and mode of action. Here, the early interactions between iron-carbohydrate nanomedicines and blood components are investigated using time-resolved small-angle X-ray and neutron scattering (SAXS and SANS, respectively) under flow conditions enabled by a microfluidic device. Two clinically relevant iron-carbohydrate complexes with different carbohydrate ligand morphologies, iron sucrose (IS) and ferric carboxymaltose (FCM), were studied for their early interactions (down to minutes) with human serum albumin (HSA) and human blood serum (HBS). When mixed with HSA, IS showed rapid agglomeration behavior at the nanoscale, as evidenced by a characteristic up-turn in the low-q region of the scattering curves, whereas FCM showed much slower agglomeration. With HBS, IS displayed a similar agglomeration behavior to that observed with HSA. In contrast, FCM showed increasingly repulsive interactions amongst its clusters in blood serum, reflected by a characteristic down-turn in the low-q scattering, associated with improved colloidal stability. These results demonstrate that early nano-bio interactions are strongly formulation-dependent and governed by differences in the carbohydrate shell architecture. These findings provide a physicochemical framework for the design of future cell-based and mechanistic studies aimed at bridging physicochemical properties with clinical outcomes.

Nanoparticle-protein dispersions constitute complex soft materials in which competing attractive and repulsive interactions can strongly influence their phase behavior, including gelation. In this work, we demonstrate a strategy to utilize interaction between anionic silica nanoparticles and anionic protein bovine serum albumin to achieve heat-induced gels with tunable physical properties. Upon heating, the protein molecules in solution undergo unfolding followed by hydrophobic aggregation, leading to the formation of a three-dimensional gel network. The introduction of negatively charged nanoparticles generates additional electrostatic repulsion that competes with the attractive hydrophobic interactions between partially unfolded proteins. This competition modifies both the structure and mechanical properties of the resulting gels. In particular, nanoparticle-protein gels exhibit markedly enhanced optical transparency (∼90%) compared with gels formed from pure protein solutions (<1%). Rheological measurements further show shear-thinning behavior, with the gel strength decreasing systematically with increasing nanoparticle concentration, leading to progressively softer gels. At sufficiently high nanoparticle content, gelation is completely suppressed, thereby stabilizing the protein dispersion against thermal aggregation. The underlying mechanism is elucidated in terms of interaction potentials obtained by modeling small-angle neutron scattering data measured in situ during gel formation. Finally, we demonstrate that nanoparticle concentration and ionic strength serve as effective parameters to control gel opacity and mechanical rigidity, enabling the formation of both soft and rigid gels. These results demonstrate how nanoparticle-mediated interactions can regulate aggregation and gelation in protein-based soft matter systems.

Nanoparticle-polymer composites offer versatile platforms for engineering tunable soft materials with tailored structural and functional properties. The anionic silica nanoparticles dispersed in polymer solutions exhibit a remarkable reentrant phase behavior, where interparticle interactions evolve from repulsive to attractive and back to repulsive (or less attractive) with increasing polymer concentration. This evolution of interaction is accompanied by a corresponding rise and subsequent fall in the hydrodynamic size and viscosity of the system, reflecting a transition from stable to aggregated state followed by restabilization. We show that the phase boundaries of this behavior can be effectively tuned by adjusting the nanoparticle concentration and/or ionic strength. Increasing nanoparticle concentration shifts the attractive regime to higher polymer concentrations, while elevated ionic strength broadens this regime. Such tuning of phase boundaries enables precise control and targeted attainment of stable or aggregated states in nanoparticle-polymer systems. The systems are examined by dynamic light scattering, viscosity, and small-angle neutron scattering. The results demonstrate that controlled modulation of interparticle interactions (electrostatic repulsion, depletion attraction and stabilization) through nanoparticle, polymer, and salt concentrations offers a powerful strategy for designing responsive nanoparticle-polymer complexes.

Heating of globular protein solutions usually leads to protein denaturation and subsequent gelation at high temperatures. Under "cold gelation", protein forms a gel at a much lower temperature than its original gelation temperature (T-G), which can be achieved by modifying various physicochemical conditions such as the pH of the solution, the presence of salts, etc. In this study, we investigated the cold gelation of Bovine Serum Albumin (BSA) protein induced by ethanol and controlled by ionic surfactant, using small-angle neutron scattering (SANS), dynamic light scattering (DLS), and rheology The results show that the T-G of the protein with ethanol is systematically decreased as compared to the that of pure BSA solutions (similar to 80 degrees C), reaching similar to 60 degrees C at 10 wt% ethanol, similar to 55 degrees C at 20 wt% and finally as low as similar to 38 degrees C in presence of 30 wt% ethanol in the solution. Rheological measurements demonstrate a significant strengthening of the gel network, with the enhancement in storage modulus (G ') from similar to 20 Pa at 0 wt% to similar to 250 Pa at 30 wt% ethanol. Structural characterization reveals an increase in fractal dimension with rising ethanol content, indicating denser and more branched gel networks. Interestingly, the addition of the anionic surfactant sodium dodecyl sulfate (SDS) inhibits the alcohol-assisted cold gelation of BSA protein, depending upon the relative amount of ethanol and SDS in solution. The results are explained based on the interplay of interactions in the protein, manipulated by the presence of alcohol, elevated temperatures, and ionic surfactant. Our study highlights the tunability of gelation pathways and offers useful inputs for controlled protein gelation in biomaterial and food industry.

Many neutron techniques can greatly benefit from enhanced neutron lenses for focusing and imaging. In this work, we revisit the potential of diffractive optics for neutron beams, building on advanced high-resolution nano-lithography techniques developed for the fabrication of X-ray diffractive optics used at synchrotron facilities. We demonstrate state-of-the-art fabrication of nickel and silicon Fresnel zone plates and we report proof-of-concept experiments for full-field neutron microscopy and small angle neutron scattering. The advancement of neutron diffractive optics will open new opportunities for neutron techniques, improving both the efficiency and resolution of existing instruments.

This study investigates the structural properties of oil-in-water emulsions stabilized with pea protein using small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) techniques particularly as regards the hydration of the protein. The high protein content needed for stability (>5% w/v) is identified as being present mainly as a dispersed component in the aqueous phase contributing to network formation and increased viscosity. The hydration of the protein was distinguished through measurements with various D2O/H2O ratios. The dispersed protein is highly hydrated (75-80% water content). Additionally, pH-dependent scattering studies revealed significant structural rearrangements and aggregation of pea protein at acidic pH and around the isoelectric point, without greatly impacting emulsion stability. A range of pea protein concentrations were studied with increased amount of dispersed material in the aqueous phase at higher protein concentrations that results in smaller oil droplets and enhanced emulsion stability. Overall, these findings highlight the complex interplay between protein hydration, pH-induced changes and aggregation, and concentration on emulsion stability. This provides insights for optimizing protein-based emulsions in food applications, paving the way for novel protein-based emulsifiers.

Poly(vinylidene fluoride) (PVDF) is technologically relevant due to its thermal stability; chemical, mechanical and radiation resistance; transparency; biocompatibility; and ease of processing. Several of those applications are related to its high electroactivity, for which the β-phase of the polymer is its most renowned protagonist. In this context, extensive research has been conducted on the crystallization of PVDF in the β-phase, when processed from melt and from solution. Several decades of research have revealed that electroactive β-PVDF can be nucleated by introducing nanofillers within the polymer matrix, based on electrostatic interactions between polymer chains and fillers. However, one question persists: beyond these electrostatic interactions, on what mechanism does the nucleation of the β-phase in composites depend? This works demonstrates, through the use of small-angle neutron scattering measurements, that the answer is related to the type of fillers' agglomeration.

Nanoparticle-polymer composite gratings incorporating ultrahigh-refractive-index hyperbranched polymers as organic nanoparticles have demonstrated exceptional light optical properties, yet their potential for neutron diffraction applications remains unexplored. We report on the neutron optical properties of a holographically structured hyperbranched-polymer-dispersed nanocomposite grating at a quasi-monochromatic neutron wavelength of 2 nm. We show that neutron diffraction measurements performed at the SANS-I instrument of the Paul Scherrer Institute (Switzerland) reveal exceptionally high neutron scattering length density modulation amplitudes. These scattering length density modulation amplitudes are the highest reported to date. Very high neutron diffraction efficiency is expected with the use of thicker uniform gratings and longer neutron wavelengths, with low angular and wavelength selectivity constraints.

The scaling behavior of linear chains with reversible bonds and, in particular, its dependence on the concentration are fundamental problems of polymer physics that are not fully understood. By means of small-angle neutron scattering we investigate the conformations of reversibly bonding polymers from high dilution (where they form unimacromolecular nano-objects, usually known as single-chain nanoparticles) to crowded solutions and bulk state far above the overlap concentration (where they are expected to form a dynamic polymer network). Unlike the cases of simple linear chains with no bonds and of chains with strictly intramolecular irreversible bonds, no shrinkage is found, and the size and scaling exponent of the reversibly bonding polymers are essentially unperturbed by crowding. This is a relevant result that confirms the negligibility of many-body effects beyond the overlap concentration in crowded systems of reversibly bonding polymers and the validity of ultrasoft effective interactions for predicting their structural and phase behavior.

Understanding the molecular structure of mesoporous solid ionic systems is essential for optimizing their macroscopic properties, such as enhanced ionic transport for energy applications and improved mechanical flexibility. These systems can be synthesized efficiently using "one-pot" conditions, where mesopores form via the microphase separation of a templating ionic liquid. Furthermore, incorporating poly(ionic liquid)s can improve structural connectivity and tailor the mechanical strength of the material. We report on the structural analysis of ionic liquid and poly(ionic liquid) embedded in ionosilica matrices, employing a combination of small-angle scattering of neutrons and X-rays, isotopic substitution, and physicochemical solvent-based extraction methods. Data analysis is based on an original, quantitative comparison of scattering curves obtained under different contrast conditions. It is shown that these mesoporous systems have an unexpected molecular structure, with the ionic liquid counterions penetrating the ionosilica matrix surrounding the mesopores, their presence being confirmed by NMR spectroscopy. The poly(ionic liquid) forms patches decorating the pore walls, with tunable conformation sensitive to solvent conditions. This behavior is anticipated to be generic in self-assembled ionosilica systems, due to the separation of the ionic liquid from the matrix, while the polymer chains have affinities for both matrix and ionic liquid.

Colloidal dispersions are key in many fields of science and technology. Recently, we have shown that small molecules can stabilize dispersions of nanoscale objects, such as proteins and nanoparticles by screening their net attractive interactions. This new effect is essentially the opposite of the well-known salt screening of electrostatic interaction. Here we show that small molecule stabilization of nanoparticles is a phenomenon strongly linked to the hydrophobic content of the particles as well as to the strength of their hydrophobic attraction. We compare the effect of proline on gold nanoparticles coated with 11-mercaptoundecane sulfonate (MUS) at varying percentages of the hydrophobic ligand octanethiol (OT). We show that the larger the percentage of OT, the larger the proline stabilization effect is. We also compare the effect of proline on water dispersions of nanoparticles with that on heavy water dispersions. In the latter, the hydrophobic effect plays a bigger role. We find that in D2O, proline stabilization is larger. We also compare the effect of proline on the same MUS:OT gold nanoparticles before and after an annealing process that is known to render the particle more hydrophilic. Proline is more effective on the particles before annealing. Finally, we study the effect of proline on non-aggregating allMUS nanoparticles. We find that proline stabilization of these particles is mainly due to a reduction in the long-range attraction coefficient. Overall, we show that proline stabilizes nanoparticle dispersions more effectively as the hydrophobic attraction between nanoparticles increases.

Green crop biomass is a sustainable protein source, which can support solving global food challenges as well as improving the bioeconomy for novel food utilization. Two green biomasses -alfalfa and water lentil- known for a high protein content and their value as feed and food components were investigated for their potential in stabilizing emulsions.For interfaces in complex food systems like emulsions, the proteins from the green biomasses act similarly to other plant proteins and even to some extent to whey proteins. The extracted green biomass protein concentrates were composed of a diverse mixture of proteins: RuBisCo as the main component, enzymes like ATP subunit synthase, chlorophyll a-b binding proteins, histones and cytochromes, which all were associated as protein aggregates or protein-polyphenol complexes with sizes from 33 up to 85 nm.These multicomponent and complex green protein components were obtained in an extraction process, and proved their capability to stabilize emulsions. Key parameters are a narrow oil droplet size distribution with rather small oil droplets with a median of about 3.5 μm, a low interfacial tension with around 15 mN/m and an elastic interfacial layer with an elastic modulus of about 45 mN/m comparable to functional whey or plant proteins. The oil/water interface of the emulsion revealed a more pronounced structural rearrangement for alfalfa protein compared to water lentil proteins as quantified by small-angle neutron scattering (SANS), indicating the relevance of plant protein source to the final structure.Green biomass proteins from alfalfa and water lentil represent a novel protein source to stabilize emulsions.

We experimentally report a hitherto unseen angular anisotropy in the polarized small-angle neutron scattering (SANS) cross section of a magnetically strongly inhomogeneous material. Based on an analytical prediction using micromagnetic theory, the difference between the spin-up and spin-down SANS cross sections is expected to show a spin-disorder-induced anisotropy. The effect is particularly pronounced in inhomogeneous magnetic materials, such as nanoporous ferromagnets, magnetic nanocomposites, or steels, which exhibit large nanoscale jumps in the saturation magnetization at internal pore-matrix or particle-matrix interfaces. Analysis of the experimental neutron data constitutes a method for determining the exchange-stiffness constant. Our results for the nuclear-magnetic interference terms contained in the polarized magnetic neutron scattering cross section might also be of relevance to other neutron techniques.

Stabilizing oil-water interfaces in emulsions by plant-based proteins provides sustainable and tunable ways for designing emulsions with specific properties, for food, healthcare, and pharmaceuticals. Cruciferin, a protein from rapeseed, has great potential as green emulsifier, but details about its structure and mobility at oil-water interfaces are largely unknown. Here, these properties are studied with small angle neutron and x-ray scattering, and neutron spin echo spectroscopy, analyzed by atomistic modelling of scattering curves and coarse-grained modelling, to gain insight into interface coverage, and molecular conformation and mobility at the interface. Cruciferin assumes trimeric conformations at the interface, as in solution, but with its protrusions from the central core of the subunits ("arms") more compressed. Interfacial mobility is only marginally lower than in solution, indicating the arms still transiently extend and preserve a network, for the first time revealing the mechanism how cruciferin forms highly elastic 2d gel-like oil-water interfaces, as observed in macroscopic rheology. The high interfacial mobility may help in self-repairing non-stabilized interfacial fractions, reducing coalescence. These findings provide a deeper molecular level understanding of proteins at oil-water interfaces, which can stimulate development of new plant-based emulsion products, and contribute to the global protein transition.

The synthesis of ultrasmall poly-L-lysine (PLL) nanoparticles remains challenging using conventional nanogel preparation methods. This study investigates how the conformation of PLL precursor chains influences the resulting nanoparticle microstructure when crosslinking is performed under dilute conditions. Structural characterization by small-angle neutron scattering (SANS), complemented by dynamic light scattering (DLS) and proton nuclear magnetic resonance ($^1$H-NMR), reveals that pre-collapsing the precursor chains—achieved by adding salt or ethanol—and controlling the crosslinking density significantly affects nanoparticle size and compactness. Crosslinking in saline buffer with higher ionic strength results in smaller nanoparticles. In contrast, crosslinking in ethanol buffer solutions does not show structural changes during the reaction; however, upon buffer exchange, the nanoparticles adopt a similarly compact conformation as those prepared in saline buffer.

The phase behavior of the liquid C2D6 below and above the critical point was investigated using small-angle neutron scattering (SANS) in temperature and pressure ranges from 10 to 45 °C and 20 to 126 bar, respectively. The scattering of thermal fluctuations of the molecular density was determined and thus the gas-liquid and Widom lines. At the same time, we observed additional scattering of droplets of more densely packed C2D6 molecules above the gas-liquid line and in the supercritical fluid regime from just below the critical point for all temperatures at about ΔP = 10 bar above the Widom line. This line is interpreted as the Frenkel line. These results are consistent with our previous studies on CO2 and thus indicate a universal phase behavior for monomolecular liquids below and above the critical point. The interpretation of the Frenkel line as the lower limit of a polymorphic phase transition is in contrast to the usual interpretation as the limit of a dynamic process. The correlation lengths (ξ) of the thermal density fluctuations at the critical point and at the Widom line are determined between 20 and 35 Å and thus in the range of the droplet radius between 60 and 80 Å. These long-range fluctuations appear to suppress the formation of droplets, which can only form at about 10 bar above the critical point and the Widom line when ξ becomes smaller than 10 Å.

An interesting evolution of the re-entrant interaction has been observed in an anionic silica nanoparticle (NP)-block copolymer (P85) dispersion due to mutually competing effects of temperature and polymer concentration. It has been demonstrated that a rise in the temperature leads to an evolution of attraction in the system, which interestingly diminishes on increasing the polymer concentration. Consequently, the system exhibits a re-entrant transition from repulsive to attractive and back to repulsive at a given temperature but with respect to the increasing polymer concentration, within a selected region of concentration and temperature. The intriguing observations have been elucidated based on the temperature/concentration-dependent modifications in the interactions governing the system, as probed by contrast-variation small-angle neutron scattering. The initial transition from the repulsive to attractive system is attributed to the temperature-driven enhancement in the hydrophobicity of the amphiphilic triblock copolymer (P85) adsorbed on nanoparticles. The strength and range of this attraction are found to be more than van der Waals attraction while relatively less than electrostatic interaction. At higher polymer concentrations, the saturation of polymer adsorption on nanoparticles introduces additional steric repulsion along with electrostatic interaction between their conjugates, effectively reducing the strength of the attraction. However, with a significant increase in temperature (>75 degrees C), the attraction again dominates the system, which eventually leads to the particle aggregation at all the measured polymer concentrations (>0.1 wt %). Our study provides useful inputs to develop smart NP-polymer composites having capabilities to respond to external stimuli such as temperature/concentration variation.

The phase transition from the ripple gel phase to the interdigitated gel phase of bilayers of phosphatidylcholines (PCs) with two saturated long-chain fatty acids under high pressure was investigated by pressure-scanning microscopy, fluorometry, and dynamic light scattering (DLS) measurements. Microscopic observation for giant vesicles (GVs) of distearoyl-PC (DSPC) under high pressure showed that spherical GVs transforms significantly into warped and distorted spherical ones instantaneously at the pressure-induced interdigitation. The fluorescence intensities of amphiphilic probe Prodan and hydrophobic probe Laurdan in the dipalmitoyl-PC (DPPC) bilayer steeply decreased and increased, respectively, at the interdigitation, suggesting that the conformational change of the polar head group of DPPC molecule in the bilayer transiently occurred at the interdigitation. Further, it was found from the high-pressure DLS measurements that the size of the vesicle particles of the DPPC and DSPC transiently increases near the interdigitation pressure, whereas the chemically induced interdigitation by adding ethanol to the DSPC bilayer membrane under atmospheric pressure produce no such change in the particle size. Taking account of the critical packing parameter of the PC molecule, the above experimental results would lead us to the conclusion that the pressure-induced interdigitation is attributable to the increase in repulsive interaction between the polar head groups of the PC molecules resulting from the orientational change of the head group from a parallel alignment to a perpendicular one with respect to the bilayer surface by applying pressure, namely the transient state: it occurs when the repulsive interaction exceeds a threshold value for the balance between the repulsive interaction and the attractive interaction among the hydrophobic acyl chains.