Small-angle neutron scattering differentiates molecular-level structural models of nanoparticle interfaces.

The highly anisotropic and nonadditive nature of nanoparticle surfaces restricts their characterization by limited types of techniques that can reach atomic or molecular resolution. While small-angle neutron scattering (SANS) is a unique tool for analyzing complex systems, it has been traditionally considered a low-resolution method due to its limited scattering vector range and wide wavelength spread. In this article, we present a novel perspective on SANS by showcasing its exceptional capability to provide molecular-level insights into nanoparticle interfaces.

Salt-Induced Linker Dehydration Modulates Micellar Structure in Ether-Linked Sulfate Surfactants.

Ether-linked surfactants are widely used in formulations such as liquid soaps, but despite their ubiquity, it is unclear how -ethylene glycol linkers in surfactants, such as sodium lauryl -(ethylene glycol) sulfate (SLEnS), influence micellar packing in the presence of NaCl. In the present work, we probe the structure and hydration of ether linkers in micelles comprising monodisperse SLEnS surfactants using contrast-variation small-angle neutron scattering (CV-SANS) and small-angle X-ray scattering (SAXS). Using SAXS, changes in micellar structure were observed for SLEnS ( = 1, 2, or 3) arising from the extent of ethoxylation.

Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes.

High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoA-I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA-I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease.

Molecular interactions with bilayer membrane stacks using neutron and X-ray diffraction.

Lamellar unit cell reconstruction from neutron and X-ray diffraction data provides information about the disposition and position of molecules and molecular segments with respect to the bilayer. When supplemented with the judicious use of molecular deuteration, the technique probes the molecular interactions and conformations within the bilayer membrane and the water layer which constitute the crystallographic unit cell. The perspective is model independent, and potentially, with a higher degree of resolution than is available with other techniques.

Terminal Deuterium Atoms Protect Silicon from Oxidation.

In recent years, the hybrid silicon-molecular electronics technology has been gaining significant attention for applications in sensors, photovoltaics, power generation, and molecular electronics devices. However, Si-H surfaces, which are the platforms on which these devices are formed, are prone to oxidation, compromising the mechanical and electronic stability of the devices. Here, we show that when hydrogen is replaced by deuterium, the Si-D surface becomes significantly more resistant to oxidation when either positive or negative voltages are applied to the Si surface.

Deuterated squalene and sterols from modified .

Uniformly deuterated sterols and biosynthetically related materials are important for neutron, NMR, tracing and bioanalysis studies as well as critical tools for the creation of improved lipid nanoparticle formulations. The production of sufficient quantities of materials relies not only on the engineering of microorganisms to selectively accumulate desired materials but also methods for the isolation, purification and characterisation of these materials to ensure their usefulness. Uniformly deuterated squalene, the universal precursor to sterols in biological systems, has been produced and characterised.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner.

There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function.

Investigation on the relationship between lipid composition and structure in model membranes composed of extracted natural phospholipids.

Hypothesis: Unravelling the structural diversity of cellular membranes is a paramount challenge in life sciences. In particular, lipid composition affects the membrane collective behaviour, and its interactions with other biological molecules.

Experiments: Here, the relationship between membrane composition and resultant structural features was investigated by surface pressure-area isotherms, Brewster angle microscopy and neutron reflectometry on in vitro membrane models of the mammalian plasma and endoplasmic-reticulum-Golgi intermediate compartment membranes in the form of Langmuir monolayers.

Structural Characterization of Nanoparticle-Supported Lipid Bilayer Arrays by Grazing Incidence X-ray and Neutron Scattering.

Arrays of nanoparticle-supported lipid bilayers (nanoSLB) are lipid-coated nanopatterned interfaces that provide a platform to study curved model biological membranes using surface-sensitive techniques. We combined scattering techniques with direct imaging, to gain access to sub-nanometer scale structural information on stable nanoparticle monolayers assembled on silicon crystals in a noncovalent manner using a Langmuir-Schaefer deposition. The structure of supported lipid bilayers formed on the nanoparticle arrays via vesicle fusion was investigated using a combination of grazing incidence X-ray and neutron scattering techniques complemented by fluorescence microscopy imaging.

The Kinetics of Aragonite Formation from Solution via Amorphous Calcium Carbonate.

Magnesium doped Amorphous Calcium Carbonate was synthesised from precursor solutions containing varying amounts of calcium, magnesium, HO and DO. The Mg/Ca ratio in the resultant Amorphous Calcium Carbonate was found to vary linearly with the Mg/Ca ratio in the precursor solution. All samples crystallised as aragonite.

Deuteration for biological SANS: Case studies, success and challenges in chemistry and biology.

Small angle neutron scattering is a powerful complementary technique in structural biology. It generally requires, or benefits from, deuteration to achieve its unique potentials. Molecular deuteration has become a mature expertise, with deuteration facilities located worldwide to support access to the technique for a wide breadth of structural biology and life sciences.

Quantitative High-Field NMR- and Mass Spectrometry-Based Fatty Acid Sequencing Reveals Internal Structure in Ru-Catalyzed Deuteration of Docosahexaenoic Acid.

Ru-based catalysis results in highly unsaturated fatty acid (HUFA) ethyl esters (EE) deuterated to various extents. The products carry H (D) mainly at their -allylic positions, where they are resistant to autoxidation compared to natural HUFA and are promising as neurological and retinal drugs. We characterized the extent of deuteration at each allylic position of docosa-4,7,10,13,16,19-hexaenoic acid deuterated to completion at -allylic and allylic positions (D-DHA) by two-dimensional (2D) and high-field (600 and 950 MHz) NMR.

Human myelin proteolipid protein structure and lipid bilayer stacking.

The myelin sheath is an essential, multilayered membrane structure that insulates axons, enabling the rapid transmission of nerve impulses. The tetraspan myelin proteolipid protein (PLP) is the most abundant protein of compact myelin in the central nervous system (CNS). The integral membrane protein PLP adheres myelin membranes together and enhances the compaction of myelin, having a fundamental role in myelin stability and axonal support.

Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.

Coronavirus disease-2019 (COVID-19), a potentially lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes.

Mg-dependent conformational equilibria in CorA and an integrated view on transport regulation.

The CorA family of proteins regulates the homeostasis of divalent metal ions in many bacteria, archaea, and eukaryotic mitochondria, making it an important target in the investigation of the mechanisms of transport and its functional regulation. Although numerous structures of open and closed channels are now available for the CorA family, the mechanism of the transport regulation remains elusive. Here, we investigated the conformational distribution and associated dynamic behaviour of the pentameric Mg channel CorA at room temperature using small-angle neutron scattering (SANS) in combination with molecular dynamics (MD) simulations and solid-state nuclear magnetic resonance spectroscopy (NMR).

Controlling phase and rheological behaviours of hexagonal lyotropic liquid crystalline templates for nanostructural administration and retention.

Introducing polymerizable monomers into a binary hexagonal lyotropic liquid crystalline (LLC) template is a straightforward way for retaining the nanostructure but will decrease attractive intra- and inter- aggregate interactions. It is therefore crucial to understand the interfacial interactions at nanoscale after introducing the monomers but prior to polymerization. Herein, active species, poly (ethylene glycol) diacrylate (PEGDA) and 2-hydroxyethyl methacrylate (HEMA), were introduced into hexagonal LLC of dodecyl trimethylammonium bromide and water to explore the structural variables, dimensional stability, and dynamic property.

Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry.

SARS-CoV-2 spike proteins are responsible for the membrane fusion event, which allows the virus to enter the host cell and cause infection. This process starts with the binding of the spike extramembrane domain to the angiotensin-converting enzyme 2 (ACE2), a membrane receptor highly abundant in the lungs. In this study, the extramembrane domain of SARS-CoV-2 Spike (sSpike) was injected on model membranes formed by supported lipid bilayers in presence and absence of the soluble part of receptor ACE2 (sACE2), and the structural features were studied at sub-nanometer level by neutron reflection.

ApoE and ApoE Nascent-Like HDL Particles at Model Cellular Membranes: Effect of Protein Isoform and Membrane Composition.

Apolipoprotein E (ApoE), an important mediator of lipid transportation in plasma and the nervous system, plays a large role in diseases such as atherosclerosis and Alzheimer's. The major allele variants ApoE3 and ApoE4 differ only by one amino acid. However, this difference has major consequences for the physiological behaviour of each variant.

Kinetic isotope effects and synthetic strategies for deuterated carbon-11 and fluorine-18 labelled PET radiopharmaceuticals.

The deuterium labelling of pharmaceuticals is a useful strategy for altering pharmacokinetic properties, particularly for improving metabolic resistance. The pharmacological effects of such metabolites are often assumed to be negligible during standard drug discovery and are factored in later at the clinical phases of development, where the risks and benefits of the treatment and side-effects can be wholly assessed. This paradigm does not translate to the discovery of radiopharmaceuticals, however, as the confounding effects of radiometabolites can inevitably show in preliminary positron emission tomography (PET) scans and thus complicate interpretation.

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles.

Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid.

Direct localization of detergents and bacteriorhodopsin in the lipidic cubic phase by small-angle neutron scattering.

Lipidic cubic phase (LCP) crystallization methods have been essential in obtaining crystals of certain membrane proteins, particularly G-protein-coupled receptors. LCP crystallization is generally optimized across a large number of potential variables, one of which may be the choice of the solubilizing detergent. A better fundamental understanding of the behavior of detergents in the LCP may guide and simplify the detergent selection process.

The effect of deuteration on the keto-enol equilibrium and photostability of the sunscreen agent avobenzone.

The remarkable properties of deuterium have led to many exciting and favourable results in enhancing material properties, for applications in the physical, medical, and biological sciences. Deuterated isotopologues of avobenzone, a sunscreen active ingredient, were synthesised to examine for any changes to the equilibrium between the diketone and enol isomers, as well as their UV photostability and photoprotective properties. Prior to UV irradiation, deuteration of the diketone methylene/enol moiety (i.