Diamond Annual Review 2023/24

52 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 3 / 2 4 Soft CondensedMatter Science Highlights Intercepting the inflammation signal Inflammation is part of the body's normal response to infection and other stresses. In eukaryotes, mitogen-activated protein kinases (MAPKs) form signalling cascades that respond to extracellular stimuli and transmit a signal through the cell membrane and down into the nucleus, activating the genes for the inflammatory response. One of these kinases, p38ɑ, has a key role in the signalling cascade and is linked to several diseases, which makes it an important drug target. Although MAPKs have been extensively studied, their rapid interactions during the signalling cascades are challenging to explore. A team of researchers used a multidisciplinary approach - including cryo- electron microscopy (cryo-EM), small-angle X-ray scattering (SAXS), enhanced sampling molecular dynamics (MD) simulations, Bayesian modelling, hydrogen-deuterium exchange mass spectrometry, and cellular assays to investigate how MAPK p38ɑ, the final switch regulating inflammation, is activated by its upstream kinase (MKK6). The 3D structure of the complex allowed the team to identify a potential new druggable pocket - a previously unknown docking site where the two enzymes interact. Feeding the structure into molecular dynamics simulations, in collaboration with the group of Prof. Francesco Gervasio in Geneva University, offered further insights into how the two kinases interact. The SAXS data obtained at Diamond were invaluable here, too, because it shows all the different states in solution, and reveals the mechanism of the formation of the complex. Their study captures a fundamental step of cell signalling, enhances our understanding of essential steps in kinase signalling cascades and paves the way for the targeted development of new therapies to stop cytokine storms. The team is nowusing the same approach to investigate other MAPK pathways, which could ultimately lead to treatments for other diseases, such as arthritis, Alzheimer's and cancer. Juyoux, P. et al. DOI: 10.1126/science.add7859 Figure: Population of states during the assembly of p38 and MKK6 as derived from the fitting to the SAXS curve. MOFs may be the key to scavengingmechanical energy First fabricated in 2012, triboelectric nanogenerators (TENGs) are a new power-generation technology that can scavenge mechanical energy from the environment and convert it into electricity. It has the potential to convert mechanical motion - human movement, vibrations, wind and wave energy - into useful electricity. Although they offer considerable promise for powering smart sensors and wearable devices, their current low power output limits commercial development. Recent research suggests that the large surface area and excellent tunability of metal-organic frameworks (MOFs) could be exploited to enhance the electrical performance of TENGs. In this study, they synthesised nanoparticles of hydrophobic zeolitic imidazolate framework ZIF-71 and its non-porous counterpart ZIF-72 (Fig.1b), dispersing each MOF into polydimethylsiloxane (PDMS – a mechanically resilient elastomer) to produce thin composite membranes. the research team discovered that the two materials are quite different in terms of their electrical generation output. The very low-energy probes (≤10 THz, see Fig.1b) they carried out at Diamond B22 beamline explain why - they have very different terahertz modes. While ZIF-71 has a relatively open structure with cavities, ZIF-71 is much more densely packed. This molecular-level architecture dictates the nature of the vibrations, and consequently, the dielectric behaviour of the two materials is distinct. Tuning the MOF/polymer combinations offers the potential for improved electrical properties; for commercial applications, durability is also a key factor. They also demonstrated harvesting energy from oscillatory motions to power commercial microelectronics such as light emitting diodes (LEDs) and a Morse code generator. The team is also investigating non-contact modes (sliding systems), whichwould be perfect for wind and tidal energy harvesting. All of their synchrotron experiments for TENGs so far have been static, so there is the potential for operando studies in the future by leveraging synchrotron nanospectroscopy. Ye, J. et al. DOI:10.1016/j.nanoen.2023.108687. Figure: Demonstration of single-electrode mode for biomechanical energy harvesting by ZIF-72/PDMS TENG. (b) TENG-powered pedometer with Bluetooth transmission to a smart phone.