Recent experiments on a small-angle/wide-angle X-ray scattering beam line at the ESRF

Recent results using a new combined small-angle/wide-angle X-ray scattering (SAXS/WAXS) beam line at the European Synchrotron Radiation Source (ESRF) will be presented. This beam line is specifically designed to be able to handle complicated sample environments required to perform time-resolved experiments mimicking processing conditions used in material science. Besides the attention that has been given to the interfacing of these sample environments to the beam line data acquisition system also the developments in detector technology will be discussed. The influence that a high count rate and low noise WAXS detector can have on the accuracy of experimental results in polymer crystallisation will be shown. It is shown that it is feasible to detect crystalline volume fractions as low as 10(-3)-10(-4) in polymeric systems

The Importance of Free Fatty Chain Length on the Lipid Organization in the Long Periodicity Phase

The skin's barrier ability is an essential function for terrestrial survival, which is controlled by intercellular lipids within the stratum corneum (SC) layer. In this barrier, free fatty acids (FFAs) are an important lipid class. As seen in inflammatory skin diseases, when the lipid chain length is reduced, a reduction in the barrier's performance is observed. In this study, we have investigated the contributing effects of various FFA chain lengths on the lamellar phase, lateral packing. The repeat distance of the lamellar phase increased with FFA chain length (C20-C28), while shorter FFAs (C16 to C18) had the opposite behaviour. While the lateral packing was affected, the orthorhombic to hexagonal to fluid phase transitions were not affected by the FFA chain length. Porcine SC lipid composition mimicking model was then used to investigate the proportional effect of shorter FFA C16, up to 50% content of the total FFA mixture. At this level, no difference in the overall lamellar phases and lateral packing was observed, while a significant increase in the water permeability was detected. Our results demonstrate a FFA C16 threshold that must be exceeded before the structure and barrier function of the long periodicity phase (LPP) is affected. These results are important to understand the lipid behaviour in this unique LPP structure as well as for the understanding, treatment, and development of inflammatory skin conditions.Drug Delivery Technolog

The importance of ceramide headgroup for lipid localisation in skin lipid models

The stratum corneum's lipid matrix is a critical for the skin's barrier function and is primarily composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The lipids form a long periodicity phase (LPP), a unique trilayer unit cell structure. An enzyme driven pathway is implemented to synthesize these key lipids. If these enzymes are down- or upregulated as in inflammatory diseases, the final lipid composition is affected often altering the barrier function. In this study, we mimicked down regulation of enzymes involved in the synthesis of the sphingosine and CER amide bond. In a LPP lipid model, we substituted CER N-(tetracosanoyl)-sphingosine (CER NS) with either i) FFA C24 and free sphingosine, to simulate the loss of the CER amide bond, or ii) with FFA C24 and C18 to simulate the loss of the sphingosine headgroup. Our study shows the lipids in the LPP would not phase separate until at least 25% of the CER NS is substituted keeping the lateral packing and conformational ordering unaltered. Neutron diffraction studies showed that free sphingosine chains localized at the outer layers of the unit cell, while the remaining CER NS head group was concentrated in the inner headgroup layers. However, when FFA C18 was inserted, CER NS was dispersed throughout the LPP, resulting in an even distribution between the inner and outer water layers. The presented results highlight the importance of the CER NS headgroup structure and its interaction in combination with the carbon chain invariability for optimal lipid arrangement.Drug Delivery Technolog

Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

The osmotic virial coefficient $B_2$ of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that $B_2$ first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of $B_2$ is compared to experiments. Implications for protein crystallization are discussed.Comment: 43 pages, including 17 figure

Outcome of the First wwPDB Hybrid / Integrative Methods Task Force Workshop

Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, on October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models

Eye lens transparency or cold cataract: a question of protein interaction potentials

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A coarse-grained model for free and template-bound porphyrin nanorings

Coarse-grained simulation models are developed to study both template-bound and free porphyrin nanoring systems. Key interactions are modelled with relatively simple (and physically-motivated) energy functions which allow for relatively facile transfer both between different ring sizes and between the template-bound and free nanoring systems. The effects of varying the model parameters on the respective radii of gyration are determined. The effects of including different templates on the ring structure are investigated both in terms of the detailed geometry of the template and the interaction strength between the template and the metal centres in the nanorings. The role of the template-nanoring interaction strength in controlling potential ``caterpillar track'' rotational motion is discussed. The relationship of the model to experimental small-angle X-ray, exchange spectroscopy and electron spin resonance results is discussed

Different Tools to Study Interaction Potentials in γ-Crystallin Solutions: Relevance to Crystal Growth

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