Category: Advanced Photon Source (APS)

Wet planets might evolve from dry, hydrogen-rich planets

Wet planets might evolve from dry, hydrogen-rich planets

Sub-Neptunes, or exoplanets 2–4 times Earth’s radius, are abundant in our galaxy. Models indicate that these exoplanets have rocky cores (the non-volatile interior) blanketed by envelopes of either hydrogen (dry gas dwarfs) or water (water worlds). 

In our own solar system, the water worlds of Uranus and Neptune orbit far from the sun, where temperatures are low enough for water to condense. This has led to the idea that water-rich planets form in the outer orbits of planetary systems, beyond what is known as the snow or ice line. They may then migrate inwards, to orbit closer to their star.

In recent years, however, large numbers of potentially water-rich exoplanets have been discovered in very close orbits. This is difficult to reconcile with the idea that such worlds can only form beyond the snow line.

The latest research by scientists from Arizona State University, The University of Chicago and the Open University of Israel suggests that water could be produced through chemical reactions at the boundary between a dry planet’s rocky core and hydrogen-rich atmosphere. This finding calls into question the idea that a planet’s composition is linked to where it formed. 

Researchers used the resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. Their results were published in the journal Nature.

To explore the potential high pressure and temperature interactions between the hydrogen in the envelope and silicate in the core of dry planets at the core-envelope boundary, the team used the unique capabilities of the University of Chicago’s GeoSoilEnviroCARS beamline at 13-ID-D of the APS. This beamline’s high pressure, high temperature diamond anvil cell setup is designed to probe materials in-situ at extreme conditions to answer geochemical and geophysical questions across the pressure and temperature range of Earth and other planets. 

Read more on the APS website

Image: The high pressure, high temperature diamond anvil cell experiments suggest that reactions between dense hydrogen fluid and molten silicates on dry planets could generate substantial amounts of water. This hints at a potential way for dry, hydrogen-rich planets to evolve into watery worlds, challenging conventional planetary formation theory.

Faster, smarter X‑ray spectroscopy with AI

Faster, smarter X‑ray spectroscopy with AI

Artificial intelligence makes X‑ray spectroscopy five times faster, smarter and less prone to human error

Argonne team’s AI-driven method takes over the manual parts of advanced X-ray spectroscopy, reducing human error and boosting experimental speed.#

Artificial intelligence (AI) is transforming nearly every branch of science. And researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory are helping lead the way.

“There is a lot of hype around AI today in the media,” said Mathew Cherukara, a computational scientist and group leader at Argonne’s Advanced Photon Source (APS), a DOE Office of Science user facility. ​“Yet there is no question that AI can help researchers at APS and other light sources make breakthroughs in advanced chemical processes critical to American industry.”

As proof, the Argonne team has developed an AI-guided method that dramatically speeds up a widely used X-ray technique known as X-ray absorption near-edge structure (XANES) spectroscopy. It does so with far less risk of human error or damage to the sample from the X-ray beams.

This powerful analytical tool reveals the hidden chemistry inside materials important to modern life, such as batteries, catalysts and materials through which electricity flows without resistance. The team’s AI approach cuts the number of measurements previously needed by as much as 80%, with no loss of accuracy. The result is a dramatic shortening of data acquisition duration, allowing researchers to capture fast chemical changes in real time.

“Yet there is no question that AI can help researchers at APS and other light sources make breakthroughs in advanced chemical processes critical to American industry.” – Mathew Cherukara, computational scientist and group leader at Argonne’s Advanced Photon Source

Here’s how XANES works: Scientists shine X-ray beams with increasing energy onto a material. Each X-ray beam is a tiny packet of energy. When the energy is high enough to knock a tightly bound electron out of an atom, the material suddenly absorbs more X-rays. This sharp jump in absorption is called the absorption edge.

By tracking how X-ray absorption changes before, during and after this edge, researchers can watch the chemistry of a specific element unfold within a material, from how a metallic catalyst reacts with other chemicals to how the charge state of a battery element changes during cycling.

“XANES is incredibly powerful, but until now, scientists had to make dozens or even hundreds of choices about where to measure and how long to measure at each X-ray energy level,” said Shelly Kelly, an APS physicist and group leader.

Image: Artistic rendering shows new AI-guided approach capturing absorption edge from atomic structure of material analyzed by XANES at a light source.

Credit: Argonne National Laboratory

Read more on Argonne website

Argonne celebrates successful completion of the APS Upgrade

Argonne celebrates successful completion of the APS Upgrade

The U.S. Department of Energy has granted its final approval to the project, bringing the decade-plus-long effort to a close

The upgraded APS is now the brightest synchrotron X-ray light source in the world, and extraordinary new scientific experiments are underway.

The comprehensive upgrade of the Advanced Photon Source (APS) is officially completed.

The U.S. Department of Energy (DOE) has given its final approval to the APS Upgrade Project, an $815 million effort to transform the APS into the brightest synchrotron X-ray facility in the world. The effort has taken more than a decade to plan and complete and has resulted in a facility with unprecedented capabilities for scientific discovery. The APS is a DOE Office of Science user facility at DOE’s Argonne National Laboratory.

The upgraded APS now generates X-ray beams that are up to 500 times brighter than before and sports nine new experiment stations (called beamlines) built to take full advantage of those enhanced beams. Scientists have been using the revamped facility for more than a year, exploring its new capabilities for research into more durable materials (for airplane turbines and other high-stress uses), longer-lasting batteries (for laptops and cell phones) and microelectronics (for our device-driven modern lives).

Read more on the Argonne website

Image: Advanced Photon Source

Credit: Argonne National Laboratory

Novel antibiotic overcomes drug-resistant bacteria

Novel antibiotic overcomes drug-resistant bacteria

Antibiotics fight bacteria in different ways. Some kill bacteria by destroying their cell walls. Others bind to bacteria’s ribosomes, halting their ability to produce proteins. Over time, bacteria evolved defense mechanisms against these threats. One mechanism is a chemical modification of the ribosome that resembles a push pin on a chair, which interferes with the antibiotic’s ability to bind to its binding site. 

Recently a team of scientists synthesized an antibiotic that can engage such modified ribosomes by pushing the “push pin” out of the way, as shown by an X-ray crystallography structural study conducted at the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. Dubbed BT-33, the novel therapeutic is active against the deadliest and most antibiotic-resistant bacteria, known collectively as ESKAPE pathogens, as well as other gram-negative bacteria, in mice. Designed to attain its binding shape prior to binding, the antibiotic can serve as a powerful model for future antibiotics.

BT-33 belongs to a class of antibiotics called lincosamides, which bind to the ribosome and halt protein production. The primary lincosamide, clindamycin, was so widely used that bacteria developed numerous defenses against them, including acquiring new genes in healthcare settings that rendered lincosamides ineffective. Nevertheless, no new lincosamide has been approved since 1970.

The scientists behind BT-33 set out to fill that void. BT-33 is the third iteration of a molecule the team reported in Nature in 2021, called iboxamycin. It was followed by cresomycin, reported in Science, in 2024. Each iteration involved structural changes to different parts of the molecule that overall improved the molecule’s ability to bind to the ribosome. Each structural change was made possible by inventing new chemical combinations that had never existed before.

Iboxamycin, the first in the series, added a new chemical group at the top end of the clindamycin molecule. That addition alone was enough to enable iboxamycin to accomplish what clindamycin could not: It overcame the defense mechanism produced by the CFR gene.

The CFR gene, first identified in 2000, encodes a protein that installed a modification on the ribosome; much like putting a push pin on a chair, the modification makes it too uncomfortable for the antibiotic to bind. The addition of the chemical group in iboxamycin that is absent from clindamycin resulted in such a strong engagement of the drug with its “chair” that the push pin got moved out of the way.

Cresomycin, the second molecule in the series, was based on a revolutionary design hypothesis called preorganization: The scientists aimed to create a molecule that adopted its shape before binding to its target. To that end, the team added a unique ten-atom ring to the bottom, giving the molecule additional rigidity. Using NMR spectroscopy, they confirmed that the molecule in solution looked exactly the same as if it were already bound to the ribosome, confirming that their design hypothesis worked.

Cresomycin proved so powerful that it overcame the resistance of the six most resistant and dangerous bacteria, collectively given the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp).

Read more on APS website

Image: Structure of BT-33 (yellow) bound to the catalytic center of the bacterial ribosome, showing the van der Waals contact of the fluorine atom (green) of BT-33 with the nucleotides of the ribosomal RNA (cyan).

Researchers use Argonne X-rays to better understand the phases of a quantum material

Researchers use Argonne X-rays to better understand the phases of a quantum material

Understanding the mysterious properties of materials requires the ability to precisely measure the atoms of those materials as they go through changes. For example, scientists are not certain why quantum materials become superconducting at low temperatures. To find out, they need the most advanced instruments available to catch the atoms in the act. 

The Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory, is one such instrument. Or rather, it’s more than 70 such instruments, able to explore materials with a variety of X-ray techniques and, when needed, combine those techniques to deliver a more comprehensive result. 

“The integration of the improved beams, the sample environment and the combination of techniques available at the APS will make further breakthroughs with these materials possible.” – Philip J. Ryan, Argonne National Laboratory

Recently a collaboration between DOE’s SLAC National Accelerator Laboratory and Argonne used the ultrabright X-ray beams of the APS to uncover tantalizing insights about strontium titanate, a material that was once used as a diamond substitute in jewelry and now has the potential to unlock our understanding of an array of quantum behaviors.

The research team built extremely thin, flexible strontium titanate membranes and, using a sample apparatus developed by the beamline staff, stretched it, in the process turning on what is known as a ferroelectric state. In that state, the material generates its own electric field, somewhat similar to how a permanent magnet generates its own magnetic field. APS X-ray beams were able to capture the movement of the ions in the material as it was repeatedly strained to ​“tune” the material in and out of a ferroelectric state.

“Our apparatus allows us to precisely control the strain placed on the material,” said Yongseong Choi, a physicist who works at the APS. ​“That and the combination of X-ray techniques we used gave us an extraordinary insight into the behavior of this material as it transitions through controlled phases.”

The team used two beamlines at the APS. They performed linear X-ray dichroism at beamline 4-ID-Dto determine the change in the spacing between the atoms, and X-ray diffraction at beamline 6-ID-Bto determine the strain on the material. Combining these results enabled the team to precisely track the arrangement of electrons in the material as its positively charged titanium ions were separated from its negatively charged oxygen ions, creating an electric field. 

While the ability to turn on ferroelectricity — as well as superconductivity through the addition of impurities — makes strontium titanate promising for applications in next generation computing, data storage and superconducting devices, this well-known material also offers us a prototype to study fundamental quantum behaviors in a plethora of structurally similar materials.

What the research team found when they lowered the material temperature to cryogenic temperatures — lower than 200 degrees Fahrenheit below zero – was a transition into a quantum state. In this state, quantum fluctuations — random, temporary changes in energy levels — present themselves. At lower temperatures under applied strain strontium titanate began to shift to a state in which quantum fluctuations, rather than thermal motion, drove the order of nearby ions in the material.

Stretching the material is an excellent tuning parameter altering those quantum fluctuations. Introducing strain as a control element gives scientists more ways to explore the material’s properties. A better understanding of this transition could help researchers tailor strontium titanate and other quantum materials for different applications, such as microelectronic switches or capacitors.

Read more on APS website

Image: An artist’s illustration of X-ray probes of strontium titanate.

Credit: Greg Stewart/SLAC National Accelerator Laboratory

Closing a gap in the race toward HIV vaccine development

Closing a gap in the race toward HIV vaccine development

Work to develop a vaccine to protect against human immunodeficiency virus (HIV) has been underway for four decades but we still have no effective vaccine. Treatments have been developed that allow people infected with HIV to live long and healthy lives, but a vaccine could prevent new infections, affecting about 1.3 million people annually worldwide, and could potentially eradicate the disease.

Unfortunately, vaccine development has been plagued by challenges related to the evasive tactics of the virus, which mutates very quickly, and difficulties in obtaining a structure for the main envelope protein of the virus, Env, which was finally solved by electron microscopy and crystallography in 2013. HIV vaccine researchers have come to the conclusion that ideal vaccine immunogens designed to generate a protective immune response should elicit antibodies that can recognize HIV via a number of target sites on the Env protein. Broadly neutralizing antibodies to each of these sites have been identified in some people infected with HIV-1 and in some animal models but efforts to elicit this broad antibody recognition of the diverse HIV strains and subtypes in response to a vaccine have not been successful.

A recent study from a group at the Ragon Institute, Scripps Research Institute, Leipzig University, La Jolla Institute for Immunology, UC San Diego, Moderna, and Massachusetts Institute of Technology provides insights into antibody-based HIV vaccine development that could lead to the identification of vaccine immunogen candidates to elicit such broadly neutralizing antibodies.

Scripps Research investigators used resources of the National Institute of General Medical Science and National Cancer Institute Structural Biology Facility (GM/CA) at beamline 23-ID-B of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

The research started with the observation that a broadly neutralizing antibody called 10E8 has excellent HIV neutralization properties but does not recognize self-antigens. This is an undesirable feature, as earlier antibodies to this membrane-proximal external region (MPER) site did. During an immune response that leads to the development of antibodies, precursor B cells that make a certain type of antibody are activated by the antigen they recognize (e.g., a viral protein), undergo mutations that increase their affinity for the antigen, and then start expanding to produce more of these cells.

With 10E8, the researchers identified precursors of the antibody, before these affinity mutations, and engineered immunogens to specifically activate these rare 10E8-class precursor B cells. This technique is called germline targeting.

To test their new immunogens, the researchers created mice that express the 10E8-class precursor B cells, which are normally only found in humans. They found that these B cells were functioning normally in mice, but when they immunized the mice with an immunogen designed to activate their targeted 10E8-class precursors B cells, they didn’t see the expansion they had hoped for, even though they could show that the B cells had high enough affinity to be activated.

Read more on APS website

Image: Orientation of mature 10E8 Fab in relation to the MPER peptide (heavy chain, white; light chain, dark gray; MPER peptide, purple; top left) and surface rendering and positioning of the critical YxFW residues of HCDR3 (bottom left), representative GT10.2-10E8UCAH mAb in complex with a glycan-knockout (KO) version of 10E8-GT10.2 (heavy chain, yellow; light chain, dark gray; targeted MPER graft with GT mutations, purple; top center; structure aligned and oriented to the MPER peptide as in the top left) and designed binding pocket (green) and engagement of the GT10.2-10E8-UCAH mAb HCDR3 (yellow) compared to mature 10E8 HCDR3 (white; bottom center) and representative GT10.2-WT mAb in complex with 10E8-GT10.2 (heavy chain, red; light chain, dark gray; targeted MPER graft with GT mutations, purple; top right) and binding pocket (green; bottom right).

Precise 3D imaging using dark-field X-ray microscopy under a structured illumination

Precise 3D imaging using dark-field X-ray microscopy under a structured illumination

Synchrotron X-ray tomography provides scientists a powerful tool for obtaining three-dimensional, high-resolution images of ordered materials. But successfully performing synchrotron tomography typically involves a complex and tedious process. For instance, the selected sample and its containment vessel must be rotated together in tiny incremental steps under a focused X-ray beam, over a full 360-degree rotation. And during this full rotation an extremely precise alignment between the crystalline lattice and rotational axis must be continuously maintained. Failure to meet this challenging protocol frequently introduces errors that seriously degrade the tomographic images.

In pursuit of a more efficient and reliable approach, a research team recently combined dark-field X-ray microscopy (DFXM) with a technique called structured illumination. This combination allows the sample and sample environment to remain stationary throughout the imaging process, resulting in quicker setup times, faster data collection, and a more robust path to achieving high-quality 3D images. The new imaging technique was performed on a pnictide superconductor at beamline 6-ID-C of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

The experimental results demonstrate the practicality of the less complex, yet still powerful, modified DFXM technique, opening up a new approach for scientists to obtain accurate 3D imaging at sub-micrometer resolutions.

3D imaging generally entails using some sort of rotation or translation. Medical CT scanners, for example, revolve an X-ray beam and detectors around a stationary patient. During each revolution the X-rays image a “slice” of the patient’s interior, and a computer then combines multiple slices to form a three-dimensional body image.

Synchrotron tomography reverses this process by fixing the X-ray beam’s direction, which then scans an incrementally rotating sample. Unfortunately, this arrangement introduces complexities that frequently lead to imaging errors. This is partly due to the sophisticated equipment that rotates with the sample, such as containment vessels for maintaining the sample at high or low temperatures, at extreme pressures, or within high magnetic fields. A servomotor then rotates both the sample and containment vessel, a complicated arrangement that not only requires long setup times but also provides multiple paths for mechanical deviations.

Read more on APS website

Exploring the molecular relationship between glycated proteins and cancer cells

Exploring the molecular relationship between glycated proteins and cancer cells

Sugar molecules in our bodies, derived primarily from food, can spontaneously adhere to various proteins, a process called glycation. Glycation can form dangerous Advanced Glycation End Products (AGEs) that lead to various pathologies like Alzheimer’s disease and diabetes, but it can also disable proteins that help cancer cells proliferate. In the early 2000s, scientists discovered that an enzyme called fructosamine-3-Kinase (FN3K) reverses protein glycation. That has made FN3K a valuable target for drug developers hoping to control when and where glycation occurs. 

The data needed for such work has been lacking. But a new study published in Nature Communications involving high-resolution structures determined from data collected at the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory, reveals how FN3K deglycates a protein. These findings can serve as the basis for structure-based and in silico drug design targeting FN3K.

Glycation normally occurs in the bloodstream, but it can happen quickly and spontaneously wherever sugar levels are high. One place would be a tumor microenvironment, where cancer cells require the energy from sugar to proliferate. 

Proliferation of cancer cells is also aided by a protein called NRF2 (nuclear factor erythroid 2-related factor 2). This transcription factor regulates genes involved in cell growth and survival. It can both suppress and promote tumors, depending on the type of cancer and what stage it’s in. Early on, it’s thought to suppress tumors; later, it’s thought to promote them. 

When NRF2 is glycated, it loses its stability and is rendered ineffective at protecting cancer cells. But NRF2 can regain this detrimental function when the sugar is removed—deglycated—by the enzyme FN3K, according to a 2019 study. This study opened two new ways of thinking about how to limit cancer cell proliferation: targeting NRF2 directly or modulating its activity through FN3K—a back door approach that would prevent the enzyme from deglycating NRF2.

With the 2019 study in mind, the scientists behind the current research set out to explore the therapeutic potential of FN3K. They determined a series of crystal structures of human FN3K (HsFN3K) in its unbound, or apo, form. Some variation of a deglycating enzyme occurs in nearly every form of life; the human form is the only one to feature the amino acid tryptophan near its core catalytic site. 

The scientists also determined crystal structures of HsFN3K bound to an analog of glycated NRF2 and the nucleotide ATP triggering different catalytic states—ATP prior to phosphorylation, ADP following phosphorylation, and AMPPNP, an ATP analog, for comparison. The X-ray diffraction data were collected at the Northeast Collaborative Access Team (NE-CAT) beamline at 24-ID-E of the APS.

With careful scrutiny of such high-resolution structures, the team deciphered what no one had seen before. In the pre-catalytic state, the tryptophan recognized the ATP, then flipped 180 degrees. That caused a conformational change in the sugar moiety on the NRF2 analog that made it receptive to phosphorylation; addition of the phosphate destabilized the sugar half and removed it from the protein. Had the resolution been any lower, scientists would not have perceived and recognized the importance of the tryptophan flip. Analyzing their structures, they found that it did not occur with ADP or AMPPNP; it only happened with ATP. 

What about tryptophan? To investigate its role, the team substituted a different amino acid to see if deglycation would still take place. It didn’t, leading the team to hypothesize that tryptophan may function as an ATP sensor, promoting HsFN3K’s kinase activity, even though it’s not part of the usual kinase classical active site players. But one tryptophan substitution gave the opposite result—changing it to a histidine, present in several versions of this enzyme from other species, made HsFN3K unusually hyperactive.

These findings have broad implications for advancing scientific knowledge and conducting basic research. The scientists hypothesize that in humans, evolution enhanced cellular homeostasis by slowing down HsFN3K’s glycating activity through tryptophan, creating an advantageous baseline level of glycation.

As for basic research, many scientists use a derivative of ATP that doesn’t trigger phosphorylation (AMPPNP) to study how ATP interacts with proteins without bothering with catalytic reaction. Only one atom distinguishes ATP from AMPPNP, but that one atom makes all the difference in the world, according to the authors of this study. They found that AMPPNP sits slightly differently from ATP in HsFN3K, preventing the tryptophan from flipping. While they don’t believe that their findings invalidate studies using AMPPNP, they do believe that in some cases, scientists should be careful how they interpret findings. 

Read more on Argonne website

Image: A representation of the crystal structure of HsFN3K in complex with ATP and the sugar mimic substrate DMF. The typical kinase fold is shown with its N-lobe in blue and C-lobe in green. DMF is positioned next to ATP in the catalytic site, both shown in stick representation. Tryptophan W219, shown with electron density shown as a mesh, is in a flipped conformation induced by the ATP binding (top inset), while in the presence of ADP it does not flip (bottom inset). The sugar (DMF) conformation is also different in the two states, underscoring the precise placement of the molecules involved for a productive reaction and providing important mechanistic insights into glycation by FN3K.

Aggregated/jammed networks of silica nanoparticles in colloids lead to dramatic thickening

Aggregated/jammed networks of silica nanoparticles in colloids lead to dramatic thickening

A colloid is formed by evenly dispersing tiny particles in a liquid. Simple examples include corn starch suspended in water, or microscopic glass beads dispersed in glycol. A simple tabletop demonstration reveals a startling property these two colloids possess: gently push your fingers into the colloid and it flows like liquid but strike it with your fist and it suddenly solidifies. 

This abrupt liquid-to-solid transition is known as discontinuous shear thickening (DST). As the name implies, the dynamic response of the colloid abruptly transitions from a liquid to a solid when the applied shear force exceeds a critical value. The general consensus among materials scientists is that inter-particle friction is responsible for DST. But surprisingly little experimental evidence directly supports this hypothesis. 

To clarify this issue, researchers recently used X-ray photon correlation spectroscopy (XPCS) to observe the dynamics of glassy colloids subjected to varying shear forces. The results showed that when a strong shearing force is applied, it induces a congested network of colloidal particles governed by friction. The work was performed at beamline 8-ID-I of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. 

Characterizing the underlying basis of DST should allow scientists to tune the dynamic behavior of many complex fluids, with real-world applications such as reducing the energy cost for mixing materials, as well as improved braking devices and body armor.

Fluids can be categorized as either Newtonian or non-Newtonian. These two categories are distinguished by reaction to shear, which is the force applied to drive fluid motion. The viscosity (ease of flow) of a Newtonian fluid does not change as shear is applied. Water and vegetable oil are both considered Newtonian fluids, since their viscosity remains unchanged when stirred.

Non-Newtonian fluids are quite different. Some non-Newtonian fluids actually become thinner (viscosity decreases) under shear as the fluid’s interior structure breaks down during shearing. In contrast, viscosity that rises slightly or moderately with shear is called continuous shear thickening (CST), while thickening that yields a solid-like state constitutes discontinuous shear thickening, or DST.

Scientists study the dynamic behavior of fluids using a device called a rheometer, which consists of two concentric cylinders as depicted in Fig. 1a. After the gap between the cylinders is filled with a colloid, the inner cylinder spins which applies a shear force. A torque sensor then measures the force/torque. What sets this particular experiment apart from other fluid-shear experiments is that XPCS data was collected simultaneously with the rheology torque measurements.

Three distinct colloids (A, B, and C) were examined, each consisting of uniformly sized silica particles dispersed in polyetheylene glycol. Particles in sample A measured 200 nanometers across and took up 60.5% of the colloid’s volume (called the volume fraction). Sample B possessed particles 360 nanometers across with a 56% volume fraction, and sample C had 360 nm particles with a 60.5% volume fraction.

Each colloid was placed in a cylindrical shear cell and then sufficient stress was applied so that the colloid approached a state nearing either CST or DST. Upon reaching equilibrium, the shear was abruptly stopped, and each colloid was monitored via XPCS for at least an hour, producing a series of speckle patterns as shown in Fig. 1b. These speckle patterns revealed how each colloid’s movements (particle velocities) changed over time.

The most interesting discovery by the team was the observation of a slowly evolving beat pattern (or heterodyne signal) in the XPCS data that occurred with both the CST-type and DST-type fluid behavior. Such a “heterodyne signal” only arises when different particles move at different speeds within the X-ray scattering volume. These particular heterodyne signals indicated the movement of mobile colloid particles against an aggregated, or jammed, network of particles produced by shear thickening.

In summary, the XPCS data showed that both CST and DST arise in highly stressed colloids due to the creation of a stagnated network of particles interacting via friction with nearby mobile particles. Moreover, after each colloid reached equilibrium, its internal stresses plunged quickly, while the internal structure and particle motion dissipated much more slowly. The researchers note that these results may also provide new insights into other systems with slowly evolving dynamics, such as the compaction of granular particles under vibration or the compaction of crumpled sheets under stress. – Philip Koth

Read more on APS website

Newly created molecules block cytokine storm

Newly created molecules block cytokine storm

Cytokine storms are potentially life-threatening overreactions of the immune system provoked by viral infection and other “threats.” Two key players are cytokines interleukin-6 (IL-6) and interleukin-1 (IL-1). Currently available inhibitors of IL-6 and IL-1 relieve the cytokine storm associated with rheumatoid arthritis, but not with COVID-19. 

Now, scientists from the University of Washington have computationally designed protein inhibitors that may prevent the COVID-19-related cytokine storm. X-ray crystallography revealed a near-perfect match between the computational designs and their real-life counterparts, which blocked the cytokine storm in a human heart organoid. This suggests that computational design has the power to create entirely new proteins that function as viable therapeutics against the cytokine storm associated with COVID-19. 

Researchers used the resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. 

Cytokine storm became a household term during the COVID-19 pandemic. Also known as cytokine release syndrome (CRS), this process happens when the immune system grossly overreacts to a threat and produces too many inflammatory immune cells. A cytokine storm can also be triggered by certain autoimmune diseases and CAR-T cell therapy.

The major players in a cytokine storm are cytokines IL-6 and IL-1. They bind to receptors on the surface of inflammatory immune cells, among others, sending signals to the cell’s DNA. These signals may activate the cell, amplify production of more inflammatory cells, or recruit cells to various locations. During a cytokine storm associated with COVID-19, too many inflammatory cells are activated and directed to the lungs and heart, where they can destroy tissue and cause fatal organ failure.

Binding is essential to the signal being sent; if there is no binding, there is no signal, and no cytokine storm. A few drugs on the market currently inhibit IL-6 and IL-1 binding, but they are better suited for long-term conditions like rheumatoid arthritis rather than short-term, acute events like COVID-19. To fill the void, a team of scientists led by 2024 Nobel Prize winner David Baker set out to design proteins from scratch that could effectively inhibit IL-6 and IL-1 binding. 

Both IL-6 and IL-1 rely on a third protein—GP130 in the case of IL-6, and an accessory protein in the case of IL-1—to send a signal when they bind with their receptors. The scientists used Rosetta, a proprietary protein design program, to create inhibitors that would occupy (a) binding sites on the IL-6 receptor, (b) the site on GP130 where IL-6 and its receptor would bind, and (c) the site on IL-1 where it would bind to both its receptor and the accessory protein.  

After generating their initial designs, the scientists tweaked them to improve the structure and amino acid sequence, then chose the top 100,000 candidates to test experimentally. First, they expressed the designs as real-life proteins in yeast cells. Then they optimized binding affinity by mutating each of the amino acids in the proteins. Finally, they used E. coli to express the optimized proteins. 

Read more on APS website

Image: Advances in computational design tools now enable functional proteins to be created from scratch.

Shaping the future of antibiotic design

Shaping the future of antibiotic design

Bacteria and fungi have been engaged in molecular warfare for millions of years. This means they have perfected ways to get past the defenses of other organisms and have also devised ways to keep them out. This arms race was revealed in 1928 when Alexander Fleming returned from his holidays to discover a petri dish of bacteria in which a fungus had started to grow and was killing the bacteria around it. He immediately realized the potential value of these antibiotic molecules to humans for curing disease. 

Now, however, our widespread use of natural antibiotics has led to the emergence of drug-resistant bacteria and an urgent need to develop some new molecular weapons of our own. With that in mind, a research group from the University of Michigan conducted a substrate-trapping study of bacterial enzymes that make an important class of antibiotics. The research provides important new information that will facilitate the design of new enzymes to make novel antibiotics that can overcome antibiotic resistance.

The group used the resources of the National Institute of General Medical Sciences and National Cancer Institute Structural Biology Facility (GM/CA) at beamlines 23-ID-B and 23-ID-D at the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

The research focused on bacterial thioesterase (TE) enzymes that perform a critical step in a synthetic pathway to make macrolide antibiotics such as erythromycin and pikromycin. These TE enzymes temporarily attach antibiotic precursors to a nucleophilic amino acid in the TE, check the structural integrity of the precursor substrates, and then convert them to either a) a cyclic lactone molecule via nucleophilic attack by an oxygen atom in the substrate, or to b) a linear final product via attack by a water molecule. Although the structures of five TE enzymes that generate various products have been solved, the process by which a product is cyclized or hydrolyzed is poorly understood. 

To get a clearer picture of the final step in the antibiotic synthesis process that might help researchers to understand the parameters needed to make new antibiotics, the team decided to use a technique called substrate trapping to visualize the moment of decision between cyclization and hydrolysis in different TE enzymes. They used a new substrate trapping technique that incorporates a non-natural amino acid into the active site in place of the natural serine or cysteine nucleophile. The bond attaching a substrate to serine or cysteine is unstable, but the non-natural amino acid traps the reaction intermediate as a stable amide group (see Figure). 

After testing five bacterial TE enzymes to see if they could successfully incorporate the substrate trap, two of substrate trapping proteins could be purified in sufficient amounts for further testing, one that makes erythromycin and one that makes pikromycin, both cyclic antibiotics. 

Read more on APS website

Image: Model of the thioesterase enzyme active site with the cyclic substrate (purple) snugly fitted into the catalytic site of the TE (yellow). The substrate trap is represented by the blue nitrogen atom that forms a stable bond between the enzyme and substrate, preventing the substrate from leaving the site so the reaction intermediate can be studied at the molecular level. The substrate nucleophilic oxygen atom (red) is at the left end of the substrate.

Credit: Rajani Arora and Vishakha Choudhary of the University of Michigan.

Manipulating polarons in thin-film tellurene shows promise for advanced electronics

Manipulating polarons in thin-film tellurene shows promise for advanced electronics

Polarons are quantum entities that arise in crystalline solids due to interactions between electrons and quantized lattice vibrations (phonons). Characterizing polaron behavior is important to scientists because they can play an important role in solid-state phenomena such as thermoelectricity, ferroelectricity, magnetoresistance, and high-temperature superconductivity. While polarons have been extensively investigated in bulk (3D) lattices, few investigations have probed polarons in one- and two-dimensional crystalline structures.

In this research, scientists probed flakes of tellurene with thicknesses of less than 20 nanometers, using a technique called extended X-ray absorption fine structure (EXAFS) spectroscopy. This work was carried out at beamline 20-BM of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

The EXAFS measurements characterized the structural changes in tellurene as flake thickness decreased, suggesting a transition from large-to-small polarons at a thickness of 10 nanometers. The experimental results gleaned from EXAFS, along with Raman spectroscopy data, were buttressed by theoretical insights and quantitative modeling that together provide a highly developed picture of polaron behavior as tellurene thickness varies.

These new findings will aid in developing the significant potential of tellurene for various technological applications, such as use in advanced transistors and sensing devices, and as a superconducting material. More broadly, these findings will also contribute to a deeper understanding of polaron behavior in other thin-film materials.

Tellurene is a thin-film semiconductor composed of helical chains of tellurium (Te) atoms. Because these helical chains interact through weak forces, it is sometimes referred to as a “quasi-one-dimensional” material. Tellurene is appealing for use in a variety of electronic applications due to its P-type semiconductor properties, which make it suitable for creating PN junctions when paired with N-type materials.

Tellurene samples were synthesized using a hydrothermal method that immerses the source materials in a closed bath of water-based solution subjected to high heat and pressure. Tellurium atoms subsequently precipitate out of the aqueous solution onto a substrate, forming tellurene flakes of varying thicknesses. Figure 1A shows a typical flake about 10 micrometers across and 9 nanometers thick. Fig. 1B is an electron microscope image of tellurene.

Phonons can exist in thin films as well as bulk 3D crystals. Just as a photon of light is a discrete unit (quantum) of electromagnetic energy, a phonon is the quantum of vibrational energy of a crystalline lattice. In tellurene, phonons can be polarized, meaning they vibrate along a particular direction, due to tellurene’s crystalline structure (Fig. 1C).

When a phonon strongly interacts with an electron in a crystalline lattice, a quasiparticle called a polaron is formed. A quasiparticle is not an actual particle, like an atom or electron, but rather a collective excitation. However, since the interaction between an electron and phonon is quite complex, treating polarons as quasiparticles makes them easier to describe both mathematically and conceptually.

Read more on APS website

Image: Optical image (A) of a tellurene flake. Superimposed lines indicate lattice structure, while inset indicates the depth profile. A scanning transmission electron microscopy (STEM) image of tellurene (B), with lavender lines highlighting lattice structure. Red arrows in panel (C) indicate lattice vibrations of individual tellurium atoms (purple spheres). These unbalanced vibrations produce polarized phonons. Plot of polaron size versus flake thickness in (D) shows that smaller polarons (with higher vibration frequency) arise in thinner flakes. Gray squares represent experimental data, while blue and red spheres are calculated from theory. Panel (E) illustrates small and large polarons. Arrows in magnified inset depict attractive (red) and repulsive (blue) electrical forces.

Breaking boundaries in biomedicine: APS enables protein design

Breaking boundaries in biomedicine: APS enables protein design

From growth hormones to cancer drugs, small molecules play a crucial role in our health. Monitoring them is essential to keeping us healthy; it enables physicians to calculate dosages and patients to monitor their medical conditions at home, for example.

Monitoring small molecules depends on sensing where they are, and in what concentrations. While scientists have developed sensors to detect some small molecules, these sensors are used primarily in research and drug discovery and can only detect a limited range of molecules with particular qualities. There is a compelling need for sensors that can detect and signal the presence of diverse small molecules of different shapes, sizes, flexibility and polarity. 

Using artificial intelligence (AI), a team of scientists led by Nobel Prize winner David Baker at the University of Washington has created a computational method for generating proteins that bind and signal a wide range of small molecules with great effectiveness. Baker won the 2024 Nobel Prize in Chemistry for computational protein design.

The research described here, published in Science and conducted in part at the Advanced Photon Source (APS), exemplifies that approach. The APS is a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

The sensor design problem

Creating a protein sensor for small molecules is very difficult. The protein must first bind to the small molecule, then signal its presence. 

The team solved both problems with modular design strategies. Their AI-generated proteins consist of identical repeating subunits surrounding a central cavity. The cavity holds a pocket where the small molecule binds.

The subunits, being modular, are easily disassembled. In this way, the small molecule binding proteins can be treated like Lego blocks and be connected to well-established signaling proteins (such as split green fluorescent protein, or GFP), to make a full sensing protein device. When a small molecule binds in the pocket, the subunits reassemble, which leads to the signaling module sending a signal that the small molecule is present.

First step: Binding

The team chose a diverse spectrum of ligands (molecules that bind to protein receptors to send signals between cells), including cholic acid, a biomarker for liver disease; methotrexate, a cancer drug, which requires regular monitoring; thyroxine, a human hormone that indicates thyroid conditions; and a cyclic peptide.

The scientists constructed a machine learning algorithm based on AlphaFold2 (a protein structure predictor whose developers, John Jumper and Demis Hassabis, shared the Nobel Prize in Chemistry with Baker) and other machine learning protein design algorithms to generate thousands of proteins to bind the small molecules.

After computational design, the team tested the designed proteins in the laboratory and identified binders to particular ligands, following computational design and using machine learning methods to choose the best designs for experimental tests.

To confirm the accuracy of their design approach, the Baker team turned to the APS. They used the ultrabright X-ray beams to collect data on the atomic structure of the binding proteins. Using the Northeastern Collaborative Access Team (NE-CAT) beamlines at 24-ID at the APS, the team determined the structures of crystals formed from one of the designed proteins. 

“Prediction algorithms are excellent tools, but without verification of the structures, there’s no proof that the predictions match reality,” said Kay Perry of Cornell University, staff scientist at NE-CAT. ​“X-ray crystallography remains one of the best ways to make that confirmation, and the team was able to do so in this case.”

Second step: Signaling

The next challenge was turning the binding proteins into signaling proteins. The scientists took advantage of their modularity to create two different types of signaling events. 

The team built ligand-induced dimerization proteins from the binders. Linna An, the first author of this study, said the technology can be used in many health-related applications, such as regulating the release of drugs in cancer therapies.

In a different type of signaling event, the scientists fused the binding proteins to a newly designed nanopore, a protein creating a channel allowing ion flow. The fused unit was constructed in such a way that when a small molecule blocked the binding pocket, the whole nanopore was blocked, preventing the flow of ions and loss of current. Loss of current signaled the presence of the small molecule. 

Read more on APS website

Image: The crystal structure of CHD_r1 (gray) is very similar to the computational design model (colored).

Credit: Linna An, et al., Science.

Catching light-activated proteins in action

Catching light-activated proteins in action

Light is an important feature of the natural world. Many organisms have developed sophisticated systems to detect light and then convey signals to sensory systems that respond. This can be achieved through coupled systems that contain both a light-sensing chromophore and a protein that passes on the information via protein conformational changes to other domains or proteins in the system.

However, these reactions work on very fast timescales and not much is known about the structural intermediates that are involved. This information is important for understanding how these systems work and could be useful for applications such as the design of light-activated cellular sensors for research or medical treatments.

In a recent publication, a collaborative team from the Korean Advanced Institute of Science and Technology (KAIST), the Korean Center for Advanced Reaction Dynamics, and the University of Chicago reported on their findings from work conducted at the University of Chicago’s BioCARS 14-ID-B beamline at the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. Their results provide new structural and mechanistic insights to further illuminate this process.

The research focused on a light-sensing protein from the common oat plant, Avena sativa, called AsLOV2, a member of a superfamily of light-activated proteins that contain the light-oxygen-voltage (LOV) domain. These LOV domain-containing proteins detect blue light in the visible spectrum and have a conserved structure composed of five β sheets and four α helices. When blue light activates the chromophore, a covalent bond is formed between the light-sensing molecule and a cysteine amino acid on the protein. This is hypothesized to lead to protein dimerization and other conformational changes that transmit the light signal downstream.

The team used time-resolved X-ray liquidography (TRXL), a sensitive technique that can detect global conformational changes in solution on a millisecond to microsecond timescale, to analyze the light-activated transition of AsLOV2.

The structure of interest for the work was a piece of the full-length AsLOV2 protein that contained the LOV domain and two helices, A’α and Jα, that are known to be involved in the light-induced dimerization of the protein and downstream signaling. The team used a mutant–type of the protein (I427V) that has a faster recovery rate than the wild–type (WT) protein, facilitating some of the measurements. Kinetic evaluation of the TRXL data showed that light-induced transition of AsLOV2 includes ground (G), first intermediate (I1), second intermediate (I2), and final photoproduct (P) states with associated time constants (WT: 682 microseconds [μs] and 10.6 milliseconds [ms], and I427V: 130 μs and 3.4 ms).

Read more on APS website

Metastable marvel: X-rays illuminate an exotic material transformation

Metastable marvel: X-rays illuminate an exotic material transformation

A flash of light traps this material in an excited state indefinitely, and new experiments reveal how it happens.

A dry material makes a great fire starter, and a soft material lends itself to a sweater. Batteries require materials that can store lots of energy, and microchips need components that can turn the flow of electricity on and off.

Each material’s properties are a result of what’s happening internally. The structure of a material’s atomic scaffolding can take many forms and is often a complex combination of competing patterns. This atomic and electronic landscape determines how a material will interact with the rest of the world, including other materials, electric and magnetic fields, and light.

Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, as part of a multi-institutional team of universities and national laboratories, are investigating a material with a highly unusual structure — one that changes dramatically when exposed to an ultrafast pulse of light from a laser.

“Together, these complementary facilities are accelerating our understanding of metastable state creation.” — Argonne Physicist Haidan Wen

After the pulse, the material is caught in an exotic state outside of equilibrium, or stability. Called metastable, these states are an exciting and largely unexplored phenomenon in materials science, and they could find application in information storage and processing. 

The team of scientists created the metastable state in 2019 and characterized the material before and after its transition. Using a combination of advanced X-ray and ultrafast laser capabilities, their recent experiments reveal the evolution of the material’s structure during the transition. The researchers captured the entire process in detail across several orders of magnitude in time, ranging from the picosecond to microsecond scales (trillionths to millionths of a second).

In particular, the team is investigating metastability in a class of materials called ferroelectrics, which play an important role in sensing and memory applications. Understanding these transitions in ferroelectrics could eventually inform the design of materials for next-generation microelectronics.

Metastable states

“Most of the materials used in technology are in equilibrium — or their lowest energy state — so that a technology can work reliably without wild variations in performance,” said Venkatraman Gopalan, professor at Pennsylvania State University and an author on the study. ​“However, this is very restrictive, since amazing properties may lurk just beyond equilibrium.”

The challenge is that nonequilibrium states are generally short-lived. Metastable states, however, are nonequilibrium states that persist for a very long time. Diamond, for example, is a metastable state of carbon. We say they’re forever, but over the course of billions of years, diamonds decay into graphite, a more stable state of carbon. 

“It’s sort of like throwing a ball up a cliff, and instead of it returning to the ground, the ball gets stuck on a ledge on the cliff wall,” Gopalan said. If the pathway to the ground is blocked by the ledge, the ball will rest there in a metastable state.

The scientists created the starting phase in this experiment by combining alternating layers of two materials — a ferroelectric and a nonferroelectric. The configurations of the electrons within the different layers compete with each other, resulting in a swirling pattern of vortices in the electronic structure across the material. This internal frustration blocks pathways that the material might otherwise take to return to equilibrium after being excited by the laser pulse.

Read more on Argonne website

Image: Illustration of the material’s transition, with time represented from left to right. A laser pulse (left) sends the material into disorder (middle). Out of this so-called soup phase emerges a highly ordered phase called a supercrystal (right).

Credit: Argonne National Laboratory

A Close Look at a Copper-Titanium Catalyst Under CO2 Hydrogenation

A Close Look at a Copper-Titanium Catalyst Under CO2 Hydrogenation

A major facet of transitioning from fossil fuels to green and renewable energy solutions involves the removal, capture and storage of carbon dioxide (CO2) from the environment. One method is by CO2 hydrogenation, which requires a catalyst to spur the reaction, frequently including metal-oxide catalysts in which metal-support interactions (MSIs) play an important role. 

Researchers from the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, Stony Brook University, DOE’s Argonne National Laboratory and several other institutions used a suite of in situ techniques to study the behavior and structural and chemical properties of a Cu@TiOx core@shell catalyst under CO2 hydrogenation. Their work was published in ACS Catalysis.

In a core@shell structure, one type of active system (the core) is encapsulated by a shell of a different material to enhance catalytic performance. These experiments focused on an inverse oxide/metal catalyst configuration using a copper nanowire core with a titanium oxide (titania) shell. Such catalysts have been shown to offer improved stability and activity over the conventional metal/oxide arrangement.

Through the use of an entire range of in situ characterization techniques – including time-resolved experiments with X-ray absorption spectroscopy (XAS), ambient pressure X-ray photoelectron spectroscopy (AP-XPS), environmental transmission electron microscopy (E-TEM), and X-ray diffraction at the 17-BM-B beamline of the Advanced Photon Source, a DOE Office of Science user facility at Argonne – the investigators sought to achieve a comprehensive understanding of the structure and behavior of the Cu@TiOx catalyst under CO2 activation and hydrogenation, a functional picture that cannot be obtained with typical steady state studies.

The dynamic characteristics of this catalyst system became immediately evident even during the standard pretreatment used for CO2 hydrogenation, when the H2 pretreatment at temperatures of above 250 degrees Celsius resulted in cracking of the titania shell and migration of Cu particles from the core to the top of the oxide shell. This, along with other configuration changes, was caused by metal-support interactions. The migrating Cu particles are about 20-40 nm in diameter and are speckled with clusters of TiOx and Cu-Ti-Ox. With this altered structure, the system displayed highly dynamic yet wholly reversible catalytic characteristics that were dependent on temperature and chemical environment.

Read more on Argonne website

Image: E-TEM that match with the XRD results.