Food fortification with water-soluble nutrients faces several challenges including poor stability, low bioavailability, and loss during processing. We developed hybrid proteoliposomes composed of lecithin and κ-casein, that we named BoostNCaps®, as delivery vehicles for water-soluble compounds. Using lactoferrin as a model cargo, we demonstrate that BoostNCaps® form monodisperse nanocapsules (∼46 nm) with a core-shell architecture confirmed by small-angle X-ray scattering. BoostNCaps® remain stable for up to 9 months at 4 °C and protect lactoferrin through simulated gastro-intestinal digestion. Critically, BoostNCaps® exhibit κ-casein-dependent precipitation upon calcium and chymosin addition, enabling a 2.5-fold improvement in water-soluble nutrient retention in cheese compared to free addition. BoostNCaps® successfully fortified milk (up to 12-week colloidal and proteolytic stability), plant-based beverages, and acidic juices. In neutral matrices (milk, oat milk), BoostNCaps® maintained full colloidal stability, while in acidic beverages (apple juice, pH 3.5), the nanocapsules formed reversible precipitates that retained the encapsulated cargo and could be redispersed by gentle inversion. Proof-of-concept studies with encapsulated vitamin B12 with efficiencies of 47–59% demonstrated platform versatility beyond proteins. BoostNCaps® address a key gap in food fortification technology by combining protection during processing with process-responsive delivery to solid foods.

High-density lipoproteins (HDL) are crucial for cardiovascular health. HDL dysfunction is strongly linked to atherosclerosis and other diseases. Although HDL is often treated as a single entity, it comprises a spectrum of subfractions differing in size, structure, and composition. Understanding the ultrastructure and function of these subfractions is essential for uncovering the molecular mechanisms behind HDL dysfunction and improving disease risk prediction. We employed Small-Angle X-ray Scattering (SAXS) and cryogenic-electron tomography (cryo-ET) to analyze the structural features of total HDL and its subfractions: HDL2b, HDL2a, and HDL3. We present updated, detailed structural models showing that the structure of HDL changes dramatically from the smallest to the largest subfraction, with HDL3 partially exposing the core to the particle's surface. Moreover, total HDL reflects the weighted sum of its subfractions, emphasizing that analysis of total HDL alone may be misleading. HDL subfractions were also studied in serum samples from 16 individuals classified as low- or high-risk for atherosclerosis. Even though biochemical differences appeared mainly in HDL2, structural differences were most pronounced in HDL3 addressing that particle composition alone cannot fully distinguish HDL dysfunction. Multimodal analysis integrating structural and biochemical data was able to separate risk groups and revealed correlations between structural parameters and cardiovascular risk status. Our findings support the importance of analyzing HDL subfractions to uncover molecular drivers of disease risk and suggest candidate biomarkers for atherosclerosis upon validation in larger cohorts.

Understanding the plant cell wall architecture is essential for elucidating its biological function and mechanical properties. This study employs a synthetic approach using spherical core-shell capsules with shells composed of deuterated bacterial cellulose (d-BC) and pectin. The shell structure was created via a bottom-up layer-by-layer assembly onto CaCO3 templates, followed by characterization through microscopy and scattering techniques. Small-angle X-ray scattering (SAXS) and confocal laser scanning microscopy revealed increased pore sizes in hydrated d-BC/pectin shells compared to those of hydrated wood-derived cellulose nanofiber (CNF)-based shells from a previous study. Using small-angle neutron scattering (SANS) with contrast variation, structural changes of individual wall components under varying salinities (0 or 10 mM NaCl) were analyzed. The presence of NaCl selectively influenced the pectin phase, while the d-BC network retained structural stability, highlighting its robustness as a wall component. This platform provides a useful tool for testing hypotheses and advancing our understanding of cell wall porosity and composition-dependent permeability.

The mcstas_gisans framework is a collection of Python scripts and modules to facilitate the simulation of grazing-incidence small-angle neutron scattering (GISANS) experiments. This approach combines McStas instrument simulation with BornAgain sample modeling capabilities. The Monte Carlo Particle Lists format for particle trajectory allows exchange between simulations that enables seamless transition from instrument modeling to sample scattering analysis. The Python-based processing utilities handle data transformation, scaling to virtual experiment times for absolute intensities, and visualization. The required software environment is managed through Conda, ensuring reproducible deployments across platforms. This integrated approach facilitates accurate simulation and analysis and enables the comparison of the GISANS capability of different neutron scattering instruments.

Interfacial structures on the nanoscale are crucial for a wide field of applications ranging from biological membranes in life sciences through organic solar cells and industrial coatings in soft matter to hard matter structures. The latter include thin film coatings and materials such as magnetic nanoparticles and topological structures like magnetic skyrmions. Advancing such application rests on the ability to reveal structures at hidden interfaces at different length scales. Techniques like scanning probe microscopy provide information about surface structures and topology with high precision, but are limited to the probe interacting with the surface. The high penetration power of neutrons, their sensitivity to light elements and the capability to probe magnetic structures makes grazing incidence small-angle neutron scattering (GISANS) a valuable, but yet underexploited, tool for organic materials and condensed matter systems and, in particular, to study buried interfaces. Together with specular and off specular neutron reflectometry, interfacial structures on length scales from a few nanometres up to micrometres can be revealed. Apart from giving a comprehensive introduction to the GISANS technique, we will highlight the importance of interfacial layer structures in different fields and how recent developments in the surface techniques have revealed common features in a range of systems. This includes the formation, structure, and topology of the interfaces of and between materials, which are controlled by the same fundamental molecular and colloidal forces.

Atherosclerosis is the leading cause of cardiovascular diseases and remains a global health challenge. Low-density lipoproteins are crucial in atherogenesis, with plasma levels as significant independent predictors of the condition. Lipoprotein(a), Lp(a), is an LDL variant considered a stand-alone atherosclerosis predictor. Although structurally similar in composition to LDL, Lp(a) contains an additional protein, apolipoprotein(a), covalently linked to apolipoprotein-B100 via a disulfide bond. This distinguishing protein is believed to confer Lp(a) its distinctive properties, including marked heterogeneity. While many studies have structurally characterised LDL particles, Lp(a) remains understudied. In this study, we isolated LDL particles from serum of normolipidemic, healthy individuals with either low or high Lp(a) levels. Our study provides biochemical, structural and functional characterisation of low and high Lp(a)-total LDL fractions. Fourier transform infrared spectroscopy (FTIR) revealed that high Lp(a) LDL exhibited a reduced ability to remove lipids from model membranes compared to low Lp(a) LDL. However, this functional difference could not be sufficiently associated with structural differences in total LDL fractions, as determined by small-angle X-ray scattering (SAXS), except for a significant difference in the particles' core-to-shell scattering mass (SM) ratio. Western blot analysis further revealed a higher abundance of Lp(a) in a small-dense subfraction, LDL6, leading us to hypothesise that structural differences might be more evident in these subfractions than in total fractions. Supporting this hypothesis, SAXS measurements on LDL6 subfractions from two subjects, with low and high Lp(a), revealed an increased protein shell thickness in high Lp(a) LDL6, a feature not directly observed in total fractions. Our data thus suggests a key role of LDL6 in LDL dysfunction.

Supported lipid bilayers (SLBs) are crucial model membrane platforms to study the structure and dynamics of cellular membranes. Vesicle fusion (VF) is one of the most widely used approaches to forming SLBs, though it suffers from compositional limitations and substrate compatibility constraints. The solvent-assisted lipid bilayer (SALB) technique enables the possibility of forming SLBs using a wider range of membrane compositions and substrate platforms through organic-solvent-mediated bilayer assembly, yet questions remain regarding structural equivalence and potential organic solvent incorporation effects. Using neutron reflectometry (NR), we systematically compare the structure and composition of phosphatidylcholine-based SLBs formed by either VF or SALB methodologies. SALB conditions were optimized for NR solid/liquid cells, and structural characterization revealed comparable bilayer architectures between the two formation methods, although some changes in the lipid acyl chain thickness were observed. SALBs showed up to 99.2 ± 0.9% surface coverage using ultrapure water for solvent exchange, but the reproducibility of the method was poor. Enhanced-contrast NR using either deuterated lipids or solvents allowed for the quantitative detection of residual organic solvent incorporation of the SALBs, which was up to 3.3 ± 0.9 vol.% in the tail regions. Making use of 1 mM CaCl2 during solvent exchange substantially improved SALB reproducibility, reducing coverage variability from 21-30 to 2  vol.%. Validation studies using the antimicrobial peptide melittin demonstrated that membrane-peptide interactions proceeded according to established mechanisms, with peptide incorporation of 18 vol.% for the low-coverage (69.7 ± 0.8%) SALB. The quantified solvent incorporation levels and small changes in acyl chain layer thickness in the SALBs must be considered when interpreting protein-membrane interaction studies, which suggests that validation of the SALB methodology for membrane research applications requires assessment on a case by case basis.

We propose a new type of sample environment for neutron reflectometry at solid-liquid interfaces. The twin-compartment solid-liquid cell optimizes several aspects of neutron reflectometry measurements by splitting the surface of substrates currently in use at facilities into two independent samples. This approach increases the capacity of mounted samples on the stage of current neutron reflectometers by a factor of two, shortens alignment times, and enables side-by-side comparison and control experiments on identical substrates. Furthermore, it reduces sample preparation time for a variety of samples prepared by Langmuir monolayer transfer techniques, spin coating, sputter coating, ex situ self-assembly and more. We present results from three cell prototypes tested on vertical and horizontal reflectometers at ISIS and Institut Laue-Langevin.

Plant cell wall porosity regulates a number of critical functions in plants, and improved structural and molecular insights are key to understanding factors that influence porosity. Yet, measuring porosity of cell walls in the wet state is not straightforward. Here, simplified hollow core-shell structures were developed with shells composed of cellulose nanofibers (CNFs) and pectin, inspired by the composition of the plant primary cell wall. These structures were examined to evaluate the influence of salinity (sodium chloride) on shell porosity via the permeation of FITC-dextran molecules. Additionally, small angle X-ray scattering, dynamic vapor sorption and electron microscopy imaging were exploited to improve mechanistic understanding. Combined, these techniques covered the sub-nm to micron length scales, and the collective experimental results implicated that sodium chloride only mediates a small increase in pore diameter. The observed increase in FITC-dextran permeability is thus rather due to changes to charge-pairing interactions between the oppositely charged CNF and pectin, and pectin mobility. The approach developed provides a platform on which to enable other plant wall polysaccharides and external stress factors to be systematically investigated.

There is an urgent need for novel inhalable drug carriers to fight respiratory infections. Lipid-coated mesoporous silica particles (LC-MSPs) combine the biocompatibility of lipids with the aerosolization properties of micronized low-density MSPs. In this study, the abundant lung surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) was used to coat disordered MSPs by means of two methods: vesicle fusion (VF) and spray-drying (SD). FT-IR and TGA analyses indicated the presence of the lipid coating, while SEM images revealed spherical particles with a smooth, homogenous surface and no detectable lipid aggregates. Both the VF and SD methods resulted in full phospholipid coverage on the outer silica surface (>100 %). However, the VF method produced a more homogeneous coating across particles and achieved a higher lipid content compared to SD (7.0 vs 3.0 % w/w). The resulting LC-MSPs exhibited favorable aerosolization properties, enabling efficient pulmonary delivery of clofazimine, a lipophilic antitubercular drug. The DPPC coating promoted interaction with endogenous lung surfactant, which enhanced the dispersion of the particles in the alveolar environment and significantly increased drug dissolution (from 35 to 75 %). Lipid coating significantly enhances particle adhesion and penetration across the human bronchial mucus layer and into the underlying tissue. Overall, our study presents a refined formulation strategy using phospholipid-coated MSPs as a single-component dry powder carrier, offering targeted lung deposition, enhanced drug dissolution, mucoadhesion, and tissue penetration.