TAVAC: comprehensive review of currently available hemostatic products as adjunct to surgical hemostasis.

BACKGROUND: The use of hemostatic agents by general surgeons during abdominal operations is commonplace as an adjunctive measure to minimize risks of postoperative bleeding and its downstream complications. Proper selection of products can be hampered by marginal understanding of their pharmacokinetics and pharmacodynamics. While a variety of hemostatic agents are currently available on the market, the choice of those products is often confusing for surgeons. This paper aims to summarize and compare the available hemostatic products for each clinical indication and to ultimately better guide surgeons in the selection and proper use of hemostatic agents in daily clinical practice. METHODS: We utilized PubMed electronic database and published product information from the respective pharmaceutical companies to collect information on the characteristics of the hemostatic products. RESULTS: All commercially available hemostatic agents in the US are described with a description of their mechanism of action, indications, contraindications, circumstances in which they are best utilized, and expected results. CONCLUSION: Hemostatic products come with many different types and specifications. They are valuable tools to serve as an adjunct to surgical hemostasis. Proper education and knowledge of their characteristics are important for the selection of the right agent and optimal utilization.

Evaluation of cataract formation in fish exposed to environmental radiation at Chernobyl and Fukushima.

Recent studies apparently finding deleterious effects of radiation exposure on cataract formation in birds and voles living near Chernobyl represent a major challenge to current radiation protection regulations. This study conducted an integrated assessment of radiation exposure on cataractogenesis using the most advanced technologies available to assess the cataract status of lenses extracted from fish caught at both Chernobyl in Ukraine and Fukushima in Japan. It was hypothesised that these novel data would reveal positive correlations between radiation dose and early indicators of cataract formation. The structure, function and optical properties of lenses were analysed from atomic to millimetre length scales. We measured the short-range order of the lens crystallin proteins using Small Angle X-Ray Scattering (SAXS) at both the SPring-8 and DIAMOND synchrotrons, the profile of the graded refractive index generated by these proteins, the epithelial cell density and organisation and finally the focal length of each lens. The results showed no evidence of a difference between the focal length, the epithelial cell densities, the refractive indices, the interference functions and the short-range order of crystallin proteins (X-ray diffraction patterns) in lens from fish exposed to different radiation doses. It could be argued that animals in the natural environment which developed cataract would be more likely, for example, to suffer predation leading to survivor bias. But the cross-length scale study presented here, by evaluating small scale molecular and cellular changes in the lens (pre-cataract formation) significantly mitigates against this issue.

TAVAC: choledochoscopy disposable scopes, and the single-stage vs. two-stage approach to choledocholithiasis.

BACKGROUND: Previous studies have been published evaluating the benefits and drawbacks of clearing the common bile duct of stones using a single-stage approach (LCBDE + LC) versus a two-stage approach (ERCP followed by LC). These studies have demonstrated that a single-stage approach offers similar outcomes and morbidities as a two-stage approach, with the added benefit of a lower cost and shorter length of stays. However, it is significant we understand why LCBDE is not commonly performed currently and also the lapse in surgical trainee exposure and competence in LCBDE. This paper aims to address the lapse in surgical trainee exposure to LCBDE, evaluate the scopes currently available to perform LCBDE, and review current data evaluating the risks and benefits of single-stage versus two-stage approaches to. METHODS: We utilized PubMed to analyze all publications related to the various disposable scopes utilized to perform choledochoscopy. We also discuss the need for disposable scopes and how this new market niche is transforming the choledochoscopy space. RESULTS: We analyzed the data related to single-stage and two-stage approach to choledocholithiasis. We noted an overall shorter length of stay and also decreased costs in favor of a single-stage approach. CONCLUSION: A single-stage LCBDE is the most cost-effective treatment option for choledocholithiasis in patients with choledocholithiasis undergoing a cholecystectomy. In addition, single-stage approach is associated with shorter length of stay. Knowledge of the available choledochoscopes and tools available to surgeons to perform choledochoscopy is significant. The evidence does support the use of disposable choledochoscope from a cost and cross-contamination perspective. Additionally, efforts should be made to incorporate LCBDE into the teaching paradigm of surgical training programs.

Collagen pre-strain discontinuity at the bone-Cartilage interface.

The bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis (OA) progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix (ECM) constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over ~50µm) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the bone-cartilage interface may be potential factors in osteoarthritis-based degeneration.

Minimising chemical crosslinking for stabilising collagen in acellular bovine pericardium: Mechanistic insights via structural characterisations.

Chemically crosslinked acellular bovine pericardium (ABP) has been widely used in clinical practice as bioprostheses. To ensure its consistency and durability, crosslinkers are used in excess, with stability guided by indicators including the hydrothermal denaturation temperature, the enzymatic resistance and the degree of crosslinking. Yet, understanding of the intermolecular structure in collagen fibrils which imparts the intrinsic stability of the ABPs is lacking, and the discrepancies in the stability criteria in varied conditions are poorly explained. In this study, synchrotron small-angle X-ray scattering (SAXS) in combination with thermal and colorimetric methods are employed to investigate the changes in the structure and the stability of ABPs during crosslinking using glutaraldehyde (GA) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) at different concentrations. Based on the findings, a mechanism is proposed to explicate the crosslinking effects on collagen structure and the relationship between the structure and each stability indicator. At low crosslinker concentrations, the telopeptidyl-helical linkages are preferred, which cause rearrangements in the intermolecular structure of collagen, and efficiently contribute to its stabilities. Excess crosslinking is revealed by a revert trend in structural changes and the plateauing of the stabilities, assigning to the helical-helical linkages and monovalent bindings. The former would improve thermal stability but not collagenase resistance, whereas the latter have negligible effects. Overall, this study provides a mechanistic understanding of the chemical crosslinking of ABPs, which will contribute to the future development of more efficient and economically viable strategies to produce bioprostheses. STATEMENT OF SIGNIFICANCE: Chemical crosslinking imparts suitable properties to acellular bovine pericardium (ABP) for clinical applications, yet the understanding is lacking on the structure-stability relationship especially under different crosslinking conditions. Structural evidence in this study differentiates the binding sites during crosslinking in collagen fibrils at different crosslinker concentrations, highlighting the excess usage in the conventional crosslinking treatments. The mechanism based on the structure of collagen also successfully explains the dissimilarity in hydrothermal and enzymatic stabilities with varied crosslinking conditions. Future researches focusing on developing biomaterials via chemical crosslinking of ABPs would benefit from this study, for its contribution to the better understanding of the relationship of collagen structure and functions.

Parameter inversion of a polydisperse system in small-angle scattering.

A general method to invert parameter distributions of a polydisperse system using data acquired from a small-angle scattering (SAS) experiment is presented. The forward problem, i.e. calculating the scattering intensity given the distributions of any causal parameters of a theoretical model, is generalized as a multi-linear map, characterized by a high-dimensional Green tensor that represents the complete scattering physics. The inverse problem, i.e. finding the maximum-likelihood estimation of the parameter distributions (in free form) given the scattering intensity (either a curve or an image) acquired from an experiment, is formulated as a constrained nonlinear programming (NLP) problem. This NLP problem is solved with high accuracy and efficiency via several theoretical and computational enhancements, such as an automatic data scaling for accuracy preservation and GPU acceleration for large-scale multi-parameter systems. Six numerical examples are presented, including both synthetic tests and solutions to real neutron and X-ray data sets, where the method is compared with several existing methods in terms of their generality, accuracy and computational cost. These examples show that SAS inversion is subject to a high degree of non-uniqueness of solution or structural ambiguity. With an ultra-high accuracy, the method can yield a series of near-optimal solutions that fit data to different acceptable levels.

In Situ and Ex Situ X-ray Diffraction and Small-Angle X-ray Scattering Investigations of the Sol-Gel Synthesis of Fe3N and Fe3C.

Iron nitride (Fe3N) and iron carbide (Fe3C) nanoparticles can be prepared via sol-gel synthesis. While sol-gel methods are simple, it can be difficult to control the crystalline composition, i.e., to achieve a Rietveld-pure product. In a previous in situ synchrotron study of the sol-gel synthesis of Fe3N/Fe3C, we showed that the reaction proceeds as follows: Fe3O4 → FeOx → Fe3N → Fe3C. There was considerable overlap between the different phases, but we were unable to ascertain whether this was due to the experimental setup (side-on heating of a quartz capillary which could lead to thermal gradients) or whether individual particle reactions proceed at different rates. In this paper, we use in situ wide- and small-angle X-ray scattering (wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS)) to demonstrate that the overlapping phases are indeed due to variable reaction rates. While the initial oxide nanoparticles have a small range of diameters, the size range expands considerably and very rapidly during the oxide-nitride transition. This has implications for the isolation of Rietveld-pure Fe3N, and in an extensive laboratory study, we were indeed unable to isolate phase-pure Fe3N. However, we made the surprising discovery that Rietveld-pure Fe3C nanoparticles can be produced at 500 °C with a sufficient furnace dwell time. This is considerably lower than the previous reports of the sol-gel synthesis of Fe3C nanoparticles.

Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging.

Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure-function relations in keloid and other fibrotic disorders in situ.

Tomographic X-ray scattering based on invariant reconstruction: analysis of the 3D nanostructure of bovine bone.

Small-angle X-ray scattering (SAXS) is an effective characterization technique for multi-phase nanocomposites. The structural complexity and heterogeneity of biological materials require the development of new techniques for the 3D characterization of their hierarchical structures. Emerging SAXS tomographic methods allow reconstruction of the 3D scattering pattern in each voxel but are costly in terms of synchrotron measurement time and computer time. To address this problem, an approach has been developed based on the reconstruction of SAXS invariants to allow for fast 3D characterization of nanostructured inhomogeneous materials. SAXS invariants are scalars replacing the 3D scattering patterns in each voxel, thus simplifying the 6D reconstruction problem to several 3D ones. Standard procedures for tomographic reconstruction can be directly adapted for this problem. The procedure is demonstrated by determining the distribution of the nanometric bone mineral particle thickness (T parameter) throughout a macroscopic 3D volume of bovine cortical bone. The T parameter maps display spatial patterns of particle thickness in fibrolamellar bone units. Spatial correlation between the mineral nano-structure and microscopic features reveals that the mineral particles are particularly thin in the vicinity of vascular channels.

Extending synchrotron SAXS instrument ranges through addition of a portable, inexpensive USAXS module with vertical rotation axes.

Ultra-SAXS can enhance the capabilities of existing synchrotron SAXS/WAXS beamlines. A compact ultra-SAXS module has been developed, which extends the measurable q-range with 0.0015 ≤ q (nm-1) ≤ 0.2, allowing structural dimensions in the range 30 ≤ D (nm) ≤ 4000 to be probed in addition to the range covered by a high-end SAXS/WAXS instrument. By shifting the module components in and out on their respective motor stages, SAXS/WAXS measurements can be easily and rapidly interleaved with USAXS measurements. The use of vertical crystal rotation axes (horizontal diffraction) greatly simplifies the construction, at minimal cost to efficiency. In this paper, the design considerations, realization and synchrotron findings are presented. Measurements of silica spheres, an alumina membrane, and a porous carbon catalyst are provided as application examples.

Pluronic F127 thermosensitive injectable smart hydrogels for controlled drug delivery system development.

Understanding structure-property relationships is critical for the development of new drug delivery systems. This study investigates the properties of Pluronic smart hydrogel formulations for future use as injectable controlled drug carriers. The smart hydrogels promise to enhance patient compliance, decrease side effects and reduce dose and frequency. Pharmaceutically, these systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and injectability as solutions before transforming into gel matrices at body temperature. We quantify the structural changes of F127 systems under controlled temperature after flow, as experienced during real bodily injection. Empirical formulae combining the coupled thermal and shear dependency are produced to aid future application of these systems. Induced structural transitions measured in-situ by small angle x-ray and neutron scattering reveal mixed oriented structures that can be exploited to tailor the drug release profile.

Structural changes in lipid mesophases due to intercalation of dendritic polymer nanoparticles: Swollen lamellae, suppressed curvature, and augmented structural disorder.

Understanding interactions between nanoparticles and model membranes is relevant to functional nano-composites and the fundamentals of nanotoxicity. In this study, the effect of polyamidoamine (PAMAM) dendrimers as model nanoparticles (NP) on the mesophase behaviour of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) has been investigated using high-pressure small-angle X-ray scattering (HP-SAXS). The pressure-temperature (p-T) diagrams for POPE mesophases in excess water were obtained in the absence and presence of G2 and G4 polyamidoamine (PAMAM) dendrimers (29 Å and 45 Å in diameter, respectively) at varying NP-lipid number ratio (ν = 0.0002-0.02) over the pressure range p = 1-3000 bar and temperature range T = 20-80 °C. The p-T phase diagram of POPE exhibited the Lß, Lα and HII phases. Complete analysis of the phase diagrams, including the relative area pervaded by different phases, phase transition temperatures (Tt) and pressures (pt), the lattice parameters (d-spacing), the pressure-dependence of d-spacing (Δd/Δp), and the structural ordering in the mesophase as gauged by the Scherrer coherence length (L) permitted insights into the size- and concentration-dependent interactions between the dendrimers and the model membrane system. The addition of dendrimers changed the phase transition pressure and temperature and resulted in the emergence of highly swollen lamellar phases, dubbed Lß-den and Lα-den. G4 PAMAM dendrimers at the highest concentration ν = 0.02 suppressed the formation of the HII phase within the temperature range studied, whereas the addition of G2 PAMAM dendrimers at the same concentration promoted an extended mixed lamellar region in which Lα and Lß phases coexisted. STATEMENT OF SIGNIFICANCE: Using high pressure small angle X-ray scattering in the pressure range 1-3000 bar and temperature range 20-60 °C, we have studied interactions between PAMAM dendrimers (as model nanoparticles) and POPE lipid mesophases (as model membranes). We report the pressure-temperature phase diagrams for the dendrimer-lipid mesophases for the first time. We find that the dendrimers alter the phase transition temperatures (Tt) and pressures (pt), the lattice parameters (d-spacing), and the structural order in the mesophase. We interpret these unprecedented results in terms of the fluidity of the lipid membranes and the interactions between the dendrimers and the membranes. Our findings are of fundamental relevance to the field of nanotoxicity and functional nanomaterials that integrate nanoparticles and organized lipid structures.

Synergy, competition, and the "hanging" polymer layer: Interactions between a neutral amphiphilic 'tardigrade' comb co-polymer with an anionic surfactant at the air-water interface.

Understanding the structure of polymer/surfactant mixtures at the air-water interface is of fundamental importance and also of relevance to a variety of practical applications. Here, the complexation between a neutral 'tardigrade' comb co-polymer (consisting of a hydrophilic polyethylene glycol backbone with hydrophobic polyvinyl acetate grafts, PEG-g-PVAc) with an anionic surfactant (sodium dodecyl sulfate, SDS) at the air-water interface has been studied. Contrast-matched neutron reflectivity (NR) complemented by surface tension measurements allowed elucidation of the interfacial composition and structure of these mixed systems, as well as providing physical insights into the polymer/surfactant interactions at the air-water interface. For both polymer concentrations studied, below and above its critical aggregation concentration, cac, (0.2 cac and 2 cac, corresponding to 0.0002 wt% or 0.013 mM and 0.002 wt% or 0.13 mM respectively), we observed a synergistic cooperative behaviour at low surfactant concentrations with a 1-2 nm mixed interfacial layer; a competitive adsorption behaviour at higher surfactant concentrations was observed where the polymer was depleted from the air-water interface, with an overall interfacial layer thickness ~1.6 nm independent of the polymer concentration. The weakly associated polymer layer "hanging" proximally to the interface, however, played a role in enhancing foam stability, thus was relevant to the detergency efficacy in such polymer/surfactant mixtures in industrial formulations.

An introduction to classical molecular dynamics simulation for experimental scattering users.

Classical molecular dynamics simulations are a common component of multi-modal analyses of scattering measurements, such as small-angle scattering and diffraction. Users of these experimental techniques often have no formal training in the theory and practice of molecular dynamics simulation, leading to the possibility of these simulations being treated as a 'black box' analysis technique. This article describes an open educational resource (OER) designed to introduce classical molecular dynamics to users of scattering methods. This resource is available as a series of interactive web pages, which can be easily accessed by students, and as an open-source software repository, which can be freely copied, modified and redistributed by educators. The topics covered in this OER include classical atomistic modelling, parameterizing interatomic potentials, molecular dynamics simulations, typical sources of error and some of the approaches to using simulations in the analysis of scattering data.

Nuclear magnetic resonance and small-angle X-ray scattering studies of mixed sodium dodecyl sulfate and N,N-dimethyldodecylamine N-oxide aqueous systems performed at low temperatures.

Surfactant crystallisation is important in many applications in the food, consumer product and medical sectors. However, these processes are not well understood. In particular, surfactant crystallisation can be detrimental to the stability of detergent formulations, such as dish liquid products, resulting in a turbid solution that fails appearance criteria. With the rising global demand for detergent products, understanding the factors that influence formulation stability is of increasing importance. To enable industry to build more robust formulations, it is important to understand the underlying chemistry of the crystallisation process. Here, a model system containing anionic (sodium dodecyl sulfate, SDS) and amphoteric (N,N-dimethyldodecylamine N-oxide, DDAO) surfactants, at concentrations typical of dish liquid products, is studied. Variable temperature 1H nuclear magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering (SAXS) is used to probe the compositional and structural properties of this system, as a function of pH. On cooling, at pH 9, a mixture of hydrated crystals, predominately composed of SDS, and micelles containing both surfactants, have been observed prior to complete freezing. At pH 2, both surfactants appear to undergo a simultaneous phase transition, resulting in the removal of micelles and the formation of hydrated crystals of mixed composition.

A guide to high-efficiency chromium (III)-collagen cross-linking: Synchrotron SAXS and DSC study.

The inefficiency of the chromium (III)-collagen cross-linking reaction during conventional leather processing results in severe environmental pollution from the waste chromium in the effluent. A mechanistic study using synchrotron-based small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) on ThruBlu tanned leather, revealed the effect of chromium sulphate and its pre-treatments on collagen structure and stability. By pre-treating with complexing agents such as sodium formate and disodium phthalate, as well as nanoclay (sodium montmorillonite), the uniformity through bovine hide collagen matrix were improved significantly. These pre-treatments effectively reduce the reactivity of chromium during its cross-linking reaction with collagen while retaining its bound water. However, collagen pre-treated with a covalent cross-linker (glutaraldehyde) results in a decrease in both chromium-collagen cross-linking and bound water while improving uniformity. These molecular-level insights can be developed into metrics to guide us towards a more sustainable future for the leather industry.

The impact of N,N-dimethyldodecylamine N-oxide (DDAO) concentration on the crystallisation of sodium dodecyl sulfate (SDS) systems and the resulting changes to crystal structure, shape and the kinetics of crystal growth.

HYPOTHESIS: At low temperatures stability issues arise in commercial detergent products when surfactant crystallisation occurs, a process which is not currently well-understood. An understanding of the phase transition can be obtained using a simple binary SDS (sodium dodecyl sulfate) + DDAO (N,N-dimethyldodecylamine N-oxide) aqueous system. It expected that the crystallisation temperature of an SDS system can be lowered with addition of DDAO, thus providing a route to improve detergent stability. EXPERIMENTS: Detergent systems are typically comprised of anionic surfactants, non-ionic surfactants and water. This study explores the crystallisation of a three component system consisting of sodium dodecyl sulfate (SDS), N,N-dimethyldodecylamine N-oxide (DDAO), and water using wide-angle X-ray scattering (WAXS), differential scanning calorimetry (DSC) and confocal Raman microscopy. FINDINGS: The presence of DDAO lowered the crystallisation temperature of a 20 wt% SDS system. For all aqueous mixtures of SDS + DDAO at low temperatures, SDS hydrated crystals, SDS.1/2H2O or SDS·H2O, formed. SDS hydrates comprising of layers of SDS separated by water layers. DDAO tended to reside in the vicinity of these SDS crystals. In the absence of DDAO an additional intermediary hydrate structure, SDS.1/8H2O, formed whereas for mixed SDS + DDAO systems no such structure was detected during crystallisation.

Structure of lipid multilayers via drop casting of aqueous liposome dispersions.

Understanding the structure of solid supported lipid multilayers is crucial to their application as a platform for novel materials. Conventionally, they are prepared from drop casting or spin coating of lipids dissolved in organic solvents, and lipid multilayers prepared from aqueous media and their structural characterisation have not been reported previously, due to their extremely low lipid solubility (i.e.∼10(-9) M) in water. Herein, using X-ray reflectivity (XRR) facilitated by a "bending mica" method, we have studied the structural characteristics of dioleoylphosphatidylcholine (DOPC) multilayers prepared via drop casting aqueous small unilamellar and multilamellar vesicle or liposome (i.e. SUV and MLV) dispersions on different surfaces, including mica, positively charged polyethylenimine (PEI) coated mica, and stearic trimethylammonium iodide (STAI) coated mica which exposes a monolayer of hydrocarbon tails. We suggest that DOPC liposomes served both as a delivery matrix where an appreciable lipid concentration in water (∼25 mg mL(-1) or 14 mM) was feasible, and as a structural precursor where the lamellar structure was readily retained on the rupture of the vesicles at the solid surface upon solvent evaporation to facilitate rapid multilayer formation. We find that multilayers on mica from MLVs exhibited polymorphism, whereas the SUV multilayers were well ordered and showed stronger stability against water. The influence of substrate chemistry (i.e. polymer coating, charge and hydrophobicity) on the multilayer structure is discussed in terms of lipid-substrate molecular interactions determining the bilayer packing proximal to the solid-liquid interface, which then had a templating effect on the structure of the bilayers distal from the interface, resulting in the overall different multilayer structural characteristics on different substrates. Such a fundamental understanding of the correlation between the physical parameters that characterise liposomes and substrate chemistry, and the structure of lipid multilayers underpins the potential development of a simple method via an aqueous liposome dispersion route for the inclusion of hydrophilic functional additives (e.g. drugs or nanoparticles) into lipid multilayer based hybrid materials, where tailored structural characteristics are an important consideration.

Hydrophobic nanoparticles promote lamellar to inverted hexagonal transition in phospholipid mesophases.

This study focuses on how the mesophase transition behaviour of the phospholipid dioleoyl phosphatidylethanolamine (DOPE) is altered by the presence of 10 nm hydrophobic and 14 nm hydrophilic silica nanoparticles (NPs) at different concentrations. The lamellar to inverted hexagonal phase transition (Lα-HII) of phospholipids is energetically analogous to the membrane fusion process, therefore understanding the Lα-HII transition with nanoparticulate additives is relevant to how membrane fusion may be affected by these additives, in this case the silica NPs. The overriding observation is that the HII/Lα boundaries in the DOPE p-T phase diagram were shifted by the presence of NPs: the hydrophobic NPs enlarged the HII phase region and thus encouraged the inverted hexagonal (HII) phase to occur at lower temperatures, whilst hydrophilic NPs appeared to stabilise the Lα phase region. This effect was also NP-concentration dependent, with a more pronounced effect for higher concentration of the hydrophobic NPs, but the trend was less clear cut for the hydrophilic NPs. There was no evidence that the NPs were intercalated into the mesophases, and as such it was likely that they might have undergone microphase separation and resided at the mesophase domain boundaries. Whilst the loci and exact roles of the NPs invite further investigation, we tentatively discuss these results in terms of both the surface chemistry of the NPs and the effect of their curvature on the elastic bending energy considerations during the mesophase transition.