Diamond Concise Annual Review 2021/22

28 29 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 1 / 2 2 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 1 / 2 2 Soft CondensedMatter Group T he Soft Condensed Matter (SCM) Group is comprised of four beamlines at Diamond: High Throughput Small Angle X-ray Scattering (SAXS) (B21), Multimode Infrared Imaging and Microspectroscopy (MIRIAM) (B22), SAXS and Diffraction (I22) and Circular Dichroism Microspectroscopy (B23). This unique portfolio of instruments enables studies of non-crystalline materials at nano- to meso-scale resolutions that include two-dimensional thin-films (photovoltaics, OLEDs), living mammalian cells, three-dimensional matrices (metal- organic frameworks, gels, and waxes) and nanoparticles in non-crystalline states. SCM science is “the science that underpins continued improvements to quality of life” and was critical to the rapid development of the COVID vaccines from Pfizer-BioNTech and Moderna. These vaccines are lipid nanoparticles encapsulating a modified messenger RNA stabilised in a non-crystalline environment. The SCM user community is international, with nearly 70%of our peer reviewed allocated beamtime to UK users with the remaining time shared between other international users. Studies this year have included those developing new drugs that could treat cancer and muscle weakness and designing new materials to limit environmental pollution. Improving the design of new anticancer drugs Numerous pharmaceutical compounds have been developed over the years to tackle a variety of cancers. These drugs, including platinum- and palladium- based agents have aimed to improve antineoplastic activity and decrease drug resistance and deleterious side effects. However, the low bioavailability and toxicity of these so-called metallodrugs, and the development of resistance to them, remain severe limitations in cancer treatment. To overcome these drawbacks, a research team from Portugal aimed to understand the mechanisms underlying drug transport and resistance which control the agent’s biodistribution and availability at its pharmacological target. They used beamline B22 to monitor biomolecular binding and conformational rearrangements, and a combination of coherent synchrotron- radiation TeraHertz spectroscopy and inelastic neutron scattering to investigate two platinum- and palladium-polyamine agents that have yielded promising results toward some types of human cancers. Their results revealed an impact of the agents on protein structure, conformational behaviour, and overall flexibility, similar to former observations on the effect of this type of metallodrugs on DNA. These findings are expected to contribute to a better understanding of the drug’s mode of action and will assist in the design of improved anticancer agents with higher bioavailability at the target, lower acquired resistance and decreased adverse side effects. Batista de Carvalho L et al. DOI: 10.1016/j.bpj.2021.06.012 Developingmaterials to break down pollution Some pollutants such as the organophosphates used in pesticides persist in the environment. Designing self-decontaminating materials with enzymes to break down long-lasting pollutants could alleviate environmental pollution or even form smart personal protective equipment. Researchers have developed a method to incorporate enzymes into materials such as plastics or polymers by modifying the surface of an enzyme with a mixture of anionic and cationic polymer surfactants. To investigate their compatibility with manufacturing fabrication techniques, an international research team studied the protein structure to ensure the enzyme remained folded and active under the conditions required for material fabrication. The unique B23 beamline facilities offered the power and reliability to assess the protein secondary structure of the solvent-free enzymes. The beamline also allowed accurate characterisation of the thermal dependent unfolding transition of the melts above 100 °C up to 250 °C, unattainable with bench-top CD instruments. Temperature-dependent Wide-Angle X-ray (WAXS) studies were conducted on beamline I22 to investigate the transition of the conjugates from lyophilised powders to annealed melts. This research showed that these fabrication methods allowed organophosphate-degrading enzymes to retain their active structure and were reproducible, leading the way for potential commercial application. ZhangWH et al. DOI: 10.1021/ acsapm.1c00845 Developing drugs to improve muscle strength Muscle weakness caused by disease and ageing significantly impacts quality of life. Although these changes are generally associated with loss of muscle mass, the intrinsic strength of a given mass of muscle is also reduced. The basic mechanical response of a skeletal muscle cell to the electrical stimulus it receives from the central nervous system is called a twitch. The structural changes that control muscle activation can be followed by measuring the diffraction of X-rays by the motor arrays, but muscles diffract X-rays very weakly, and these experiments require an extremely bright X-ray source combined with a sensitive X-ray video camera that can record 200 diffraction patterns every second. Beamline I22 is one of few facilities worldwide that meet these demanding requirements. A team from King’s College, London was able to uncover the molecular structural factors that limit the strength of skeletal muscle in its normal twitch response. This pioneering work allows those structures to be used to design and test potential drugs that could increase muscle strength. Almost identical mechanisms operate to limit the strength of the heartbeat and could also be targeted to treat heart failure. Hill C et al. DOI: 10.7554/eLife.68211 Experimental Michelson Interferometer setup, part of the infrared nanoscope on beamline B22.