Highlights of Published Papers

Science Illustration of scientists
Image credit: Freepix

This is where you can find highlights of scientific papers published by the people of ESS. We will regularly be adding to this list, so do come back to learn more.

Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents

electrostatic repulsion

Representation of the electrostatic repulsion in deep eutectic solvents

Electrostatic interactions play an essential role in biological and technological processes. From ion motion in batteries to protein function in living cells, charge modulation dictates the function of processes that involve ions. The traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions. This research demonstrates that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. By investigating intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering, long-range electrostatic repulsions between charged colloidal particles were observed. Experiments were performed on Sans2d (ISIS Pulsed Neutron Source) and D11 (Institute Laue-Langevin).

Cite: Sanchez-Fernandez, A. et al. Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents. J. Am. Chem. Soc., 2021, 143, 35, 14158-14168 doi: doi.org/10.1021/jacs.1c04781
ESS contact: Andrew Jackson
Link: https://pubs.acs.org/doi/10.1021/jacs.1c04781

Observations of the effect of strong Pauli paramagnetism on the vortex lattice in superconducting CeCu2Si2

diffraction pattern of the vortex lattice

Before (left) and after (right) of the diffraction pattern of the vortex lattice in CeCu2Si2 measured at 130 mK and 1.5 T using Bayesian processing.

Superconductivity was first discovered over 100 years ago, but there are still many open questions. While conventional superconductors are well explained by the BCS theory, a large number of ‘unconventional superconductors’ behave differently. One example is CeCu2Si2 – the first heavy fermion superconductor to be discovered in 1979. But what does heavy fermion mean here?
In a superconductor, the charge carriers (usually electrons) pair up to form a Cooper pair. In a heavy fermion material, the charge carriers behave as though they have a mass many times that of a free electron, pushing all the energy scales in the materials lower. BCS theory cannot be applied to materials like this, and so a lot of questions remain over the superconducting state. To study this, we looked at the flux-line lattice that develops inside CeCu2Si2 when it is put in a magnetic field. Normally, a superconductor expels magnetic field, but many superconductors, like CeCu2Si2, allow magnetic flux to enter as small tubes, or flux lines, where the material is not superconducting. The rest of the material then stays superconducting up to larger fields, or with larger applied currents. We have used small-angle neutron scattering to diffract off the flux-line lattice, as the size and arrangement of the flux lines tells us about the underlying superconductivity. An example diffraction pattern is shown below, before and after processing via Bayesian methods to extract more information from the scattered neutrons. CeCu2Si2 shows a very unusual increase in flux-line intensity towards the edge of the superconducting phase, whereas in most other superconductors, this intensity drops towards zero, indicating that the superconductivity is not destroyed in the same way as in almost all other superconductors.

Cite: Campillo, E. et al., Observations of the effect of strong Pauli paramagnetism on the vortex lattice in superconducting CeCu2Si2. Phys. Rev. B, 104, 184508, 2021, doi: 10.1103/PhysRevB.104.184508
ESS contact: Alex Holmes
Link: https://journals.aps.org/prb/abstract/10.1103/PhysRevB.104.184508

New perspectives for neutron imaging through advanced event-mode data acquisition

image for highlight

Photograph (A) and Schematic (B) of the detector set up, and detection of photon and neutron events (C).

The use of scintillators and cameras is extremely widespread in the field of neutron radiography, both for its cost-effectiveness and for its simplicity. One drawback of such an approach is that the scintillator itself is the limiting factor in terms of achievable resolution and detection efficiency. Furthermore, this configuration offers very little in terms of time resolution and therefore can be used for a limited number of very specific Time-of-Flight applications. Recent developments in event-driven detectors allow the recording and reconstruction of the shape of light spots emitted by the scintillator after a single particle interaction, allowing reconstruction of the Center-of-Mass of the interaction within the scintillator. This enables a more precise localization of the single event and provides a pathway to overcome the scintillator thickness limitation and increase the effective spatial resolution of the system, while still retaining the ease of use and flexibility of traditional camera systems. The detection of single events allows also to retain the timing information, making this approach suitable for Time-of-Flight applications.

In this paper we present such a detector. We show that it is capable of Time-of-Flight imaging with an adjustable field-of-view, ad-hoc binning and re-binning of data based on the requirements of the experiment and the possibility of particle discrimination via the analysis of the event shape in space and time. We believe that this novel concept might replace regular cameras in neutron imaging detectors as it provides superior detection capabilities. We demonstrate an increase by a factor 3 in image resolution and an increase by up to a factor of 7.5 in signal-to-noise for thermal neutron imaging. Such a detector is not limited only to imaging, and new approaches to detection for diffraction experiments are also a clear outlook.

Cite: Losko, A.S., New perspectives for neutron imaging through advanced event-mode data acquisition. Sci Rep, 11, 21360, 2021, doi: 10.1038/s41598-021-00822-5
ESS contact: Manuel Morgano
Link: https://www.nature.com/articles/s41598-021-00822-5

Evlolving Escherichia coli Host Strains for Efficient Deuterium Labeling of Recombinant Proteins Using Sodium Pyruvate-d3

sodium pyruvate

Framework of production of sodium pyruvate-d3, and deuteration of recombinant proteins

Labeling of proteins with deuterium (2H) is often necessary for structural biology techniques, such as neutron crystallography, NMR spectroscopy, and small-angle neutron scattering. However, perdeuteration in which all protium (1H) atoms are replaced by deuterium is a costly process. Typically, an expression host such as Escherichia coli is grown in a defined medium (M9) with heavy water as the solvent and a deuterated carbon source such as glucose-d7 or glycerol-d8. An alternative carbon source, pyruvate, can be deuterated in-house relatively simply, but the growth of E. coli on this carbon source is very poor. To circumvent this problem, adaptive laboratory evolution was used to obtain E. coli strains with a greatly improved growth rate on pyruvate, and using pyruvate-d3 as carbon source, >90% deuterated triose-phosphate isomerase was produced in sufficient quantities for large volume crystal production and subsequent analysis by neutron crystallography.

Cite: Kelpšas, V. et al. Evolving Escherichia coli Host Strains for Efficient Deuterium Labeling of Recombinant Proteins Using Sodium Pyruvate-d3. Int. J. Mol. Sci., 2021, 22, 9678, doi: 10.3390/ijms22189678
ESS Contact: Anna Leung
Link: https://www.mdpi.com/1422-0067/22/18/9678

A protocol for production of perdeuterated OmpF porin for neutron crystallography

Schematic representation Swati

Schematic representation for production of perdeuterated OmpF

Hydrogen (1H) atoms form the basis of the hydrogen bond that is not scattered by X-ray crystallography due to its poor scattering power.  Neutron protein crystallography (NPX) is a powerful tool that is capable of locating hydrogens and study the significance of hydrogen bonding interactions in biomacromolecules. However, due to the requirement for large crystals very few neutron structures have been deposited in PDB with no membrane protein structure determined yet. Additionally, 1H has a negative scattering length and large incoherent cross-section giving rise to a significant background noise in neutron data collection. This effect can be minimised by isotopic substitution of 1H with its heavier isotope deuterium (2H or D) leading to less ambiguous data analysis and better structure interpretation.  Overall ~25% H atoms in a protein are solvent can be exchanged by dissolving in heavy water. However, complete deuterium labelling (perdeuteration) is required for the remaining 75% H atoms. In this work, an optimised methodology for large scale production of perdeuterated bacterial outer membrane protein F (OmpF) has been designed. OmpF was produced in deuterated minimal medium with different carbon sources. Mass spectrometry and thermal stability experiments verified the purity and level of deuteration of OmpF protein. We obtained protiated and perdeuterated OmpF crystals that diffracted X-rays to a resolution of 1.9 Å. No significant effect of deuterium-labelling was observed on structural properties of protein. This work lays the foundation for structural studies of membrane protein by neutron diffraction in future.

Cite: Aggarwal, S. A protocol for production of perdeuterated OmpF porin for neutron crystallography. Protein Expression and Purification, 188, 105954, 2021, doi: 10.1016/j.pep.2021.105954
ESS contact: Esko Oksanen, Zoë Fisher; Lund University contact: Claes von Wachenfeldt
Link: https://www.sciencedirect.com/science/article/pii/S1046592821001376?via%3Dihub

Overscreening and Underscreening in Solid-Electrolyte Grain Boundary Space-Charge Layers

2D schematic of the kinetic Monte Carlo model

Two-dimensional schematic of the kinetic Monte Carlo model used in this work

Solid electrolytes are ionic conductors with potential applications in next generation batteries. However, prediction of the equilibrium distribution of ions within these materials, which are crystalline solids with grain broundaries and heterointerfaces, is a long-standing problem in solid-state physics. Near to these interface regions, the concentration of individual ionic species can deviate significantly from their formal bulk values, giving rise to so-called “space-charge” regions. Using kinetic Monte Carlo simulations of a three-dimensional Coulomb lattice gas, this work has show that these space-charge regions may exhibit features similar to liquid-state materials, such as ionic liquids and concentrated electrolyes. The analysis of this work utilised Bayesian inference to compare traditional solid state dilute limit models with more complex oscillatory models. 

Cite: Dean, J.M. et al. Overscreening and Underscreening in Solid-Electrolyte Grain Boundary Space-Charge Layers. Phys. Rev. Lett., 2021, 127, 135502, doi: 10.1103/PhysRevLett.127.135502
ESS Contact: Andrew McCluskey
Link: https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.127.135502

Neutron structures of Leishmania mexicana triosephosphate isomerase in complez with reaction intermediate mimics shed light on the proton-shuttling steps

Joint X-ray/neutron structure of PGA-TIM

Triosephosphate isomerase (TIM) is a key enzyme in glycolysis that catalyses the interconversion of glyceraldehyde 3-phosphate and dihydroxy­acetone phosphate. This simple reaction involves the shuttling of protons mediated by protolysable side chains. It is an example of the case of an enzyme mechanism where a long-standing controversy between competing models of proton movements can be resolved by neutron crystallography. The structures presented show that with the transition state analogue 2-phosphoglycolate (PGA) the postulated general base Glu167 is protonated, confirming Glu167 as the general base. The deuteron is clearly localised on Glu167, suggesting an asymmetric hydrogen bond instead of a low-barrier hydrogen bond. The full picture of the active-site protonation states allowed an investigation of the reaction mechanism using density-functional theory calculations.

Cite: Kelpšas V. et al. Neutron structures of Leishmania mexicana triosephosphate isomerase in complex with reaction-intermediate mimics shed light on the proton-shuttling steps. IUCrJ, 8(4), 633-643. 2021. doi:10.1107/S2052252521004619
ESS Contact: Esko Oksanen
Link: Paper - https://doi.org/10.1107/S2052252521004619
Link: Commentary - https://doi.org/10.1107/S205225252100573X

Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/16

Magnification of one of the SARS-CoV-2 nsp10 binding sites

Magnification of one of the SARS-CoV-2 nsp10 binding sites overlapping with residues of nsp14. The bound fragment is coloured in green.

In March 2020, the Deuteration and Macromolecular Crystallisation (DEMAX) groups at the ESS issued a special call for proposals related to Covid-19 research. One of the projects has led to a larger collaboration between DEMAX, Frank Kozielski (University College London), and Wolfgang Knecht (Lund Protein Production Platform, LP3, at Lund University) and now the FragMAX platform of the MAX IV laboratory. The project is to find small molecule inhibitors that can block the SARS CoV-2 replication machinery. Non-structural protein 10 (nsp10) is a conserved stimulator of two enzymes crucial for viral replication, nsp14 and nsp16, exhibiting exoribonuclease and methlytransferase activities. Interfering with RNA proofreading or RNA cap formation represents intervention strategies that can be exploited to inhibit viral replication. Fragment-based screening using nano differential scanning fluorometry, x-ray crystallography and hit confirmation by microscale thermophoresis was carried out to identify ligands and measure their binding affinities to SARS-CoV-2 nsp10. Four fragments were identified that were found to bind to two distinct binding sites on nsp10: one can be modelled to where it would be located in the nsp14-nsp10 interface (Figure 1) and the other to the protein-protein interace of the nsp16-nsp10  complex. These fragments now serve as starting points for the development of more potent analogues using fragment growing techniques and structure-based drug design. This research used unique capabilities found at FragMAX and the BioMAX beamline, accessing a fragment library and making use of prioritized access to the BioMAX beamline, all during the ongoing pandemic

Cite: Kozielski F. et al. Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/16. RSC Chemical Biology, 2021, doi:10.1039/D1CB00135C
ESS Contact: Zoë Fisher; LP3 Contact: Wolfgang Knecht; UCL Contact: Frank Kozielski; FragMAX Contact: Tobias Krojer
Link: https://pubs.rsc.org/en/content/articlelanding/2021/cb/d1cb00135c

Stripping mechanisms and remediation for H- beams

Radial dependence of blackbody radiation photon counts (normalized by 1/r) in a circular pipe

Radial dependence of blackbody radiation photon counts (normalized by 1/r) in a circular pipe

The H- ion is often used for the accumulation of high-intensity proton populations in storage rings. This is done by stripping both its electrons (using either thin intercepting foils or laser stimulation) and bringing them into orbit with a circulating proton bunch. In doing so, higher intensities can be extracted from a ring than would be possible by simply injecting protons. The difficulty is reaching the ring: H- tends to have its weakly bound outer electron easily stripped away prior to the injection stage. This produces a neutral hydrogen atom, which follows a drift trajectory to ultimately collide and deposit most of its energy into external components, causing unwanted induced radioactivity.  In this work, we summarize the theory governing the various types of stripping, from interaction with external fields or blackbody radiation, to collisions with adjacent H- ions. Simulated results are shown for practical test cases, where we demonstrate that the large majority of stripped hydrogen atoms deposit their energy into a final line-of-sight beam dump at the end of a linac or straight section, potentially relaxing the concerns for induced radioactivity of beam-line components.

Cite: Folsom B.T. et al. Stripping mechanisms and remediation for H- beams. Phys Rev Accel Beams 24, 074201, doi: 10.1103/PhysRevAccelBeams.24.074201
ESS Contact: Ben Folsom
Link: paper - https://link.aps.org/doi/10.1103/PhysRevAccelBeams.24.074201
Link: project video - https://www.youtube.com/watch?v=qAnvft0nAlg

Emergent magnetic behaviour in the frustrated Yb3Ga5O12 garnet

Emergent Magnetic behaviour paper: ResearchStudents

PhD students on experiment celebrating their experimental success. Left to right: Richard Edberg (KTH), Lise Sandberg (KU) and Ingrid-Marie Bakke (Oslo University).

Published 13 August 2021: Quintessential frustrated magnetic materials are those based on a triangular hyperkagome crystalline lattice and include the isostructural compounds Gd3Ga5O12 (GGG) and Yb3Ga5O12 (YGG). Our previous studies (Science 350, 6257 (2015)) uncovered a most unusual long range emergent director state in GGG derived from magnetic spins arranged on a ten-ion loop despite a disordered state at the local level. In this most recent work we show that the director state is also found in YGG, albeit correlated over a much reduced distance, revealing the ubiquity of this unusual state of matter. Neutron scattering experiments were performed on single crystal YGG, using the polarised diffuse scattering spectrometer, D7, at the ILL, the cold neutron scattering spectrometer, CNCS at the SNS and the thermal chopper spectrometer, IN4 at the ILL. An understanding of these novel states of matter in magnetic materials will result in technological breakthroughs beneficial to our spintronic society.

PHD students: R.Edberg (KTH), L: Sandberg (KU-ESS) and I.M. Bakke (Oslo University-ESS), supervised by Pascale Deen, Senior Scientist for Spectroscopy at ESS, Pascale Deen, and Adjunct Associate Professor, Niels Bohr Institute , University of Copenhagen.

Cite: Sandberg, L. Ø. et al. Emergent behavior in the frustrated Yb3Ga5O12 garnet. Phys. Rev. B. 104, 064425, doi:10.1103/PhysRevB.104.064425 (2021). 
ESS Contact: Pascale Deen
Link: https://journals.aps.org/prb/abstract/10.1103/PhysRevB.104.064425