A poison helps us understand molecular hydrogen-producing biocatalysts

A poison helps to understand molecular hydrogen-producing biocatalysts
Superimposition of structures of CpI in various states. Credit: Angewandte Chemie International Edition (2022). DOI: 10.1002/anie.202216903

In nature, enzymes termed hydrogenases are capable of producing molecular hydrogen (H2). Special types of these biocatalysts, so-called [FeFe]-hydrogenases, are extremely efficient and therefore of interest for biobased hydrogen production. Although scientists have learned a lot about how these enzymes work, many details remain to be completely understood.

A research team of the Photobiotechnology group at Ruhr University Bochum, Germany, headed by Dr. Jifu Duan and Professor Thomas Happe succeeded in filling a scientific gap. The researchers showed that external cyanide binds to the [FeFe] hydrogenases and inhibits hydrogen formation. In the process, they detected a structural change in the proton transport pathway, which helps to understand the coupling of electron and proton transport. They reported their findings in the journal Angewandte Chemie of December 4, 2022.

A sophisticated internal catalyst

To generate H2, these biocatalysts transfer electrons to protons, employing a sophisticated structure as internal catalyst. This so-called H-cluster contains electronically active iron ions that are bound to what most people know as toxins: carbon monoxide and cyanide.

However, although internal carbon monoxide and cyanide are crucial for the high activity of hydrogenases, additional external carbon monoxide binds to the H-cluster and prevents its H2 production. “Interestingly, cyanide is also a well-known inhibitor of iron-containing biocatalysts,” says Jifu Duan. “And yet, its effect on [FeFe]-hydrogenases has hardly been analyzed before.”

The Bochum-based research team closed this scientific gap. The researchers showed that external cyanide binds to and inhibits [FeFe]-hydrogenases. In collaboration with Professor Eckhard Hofmann, head of the protein crystallography group at RUB, the team obtained the structure of H2-producing biocatalysts to which external cyanide was bound.

“The high-resolution structure in combination with spectroscopic analyses tells us that the external cyanide directly binds to the H-cluster, similar to other inhibitors studied so far,” says Jifu Duan. “This explains why the hydrogenase is inactive after cyanide treatment.”

Coincidental capture of a transient state

When the researchers took a detailed look into the structure of the cyanide-poisoned hydrogenase, they found a surprise. They observed structural changes in the proton transport pathway that is required to guide the protons that will become H2 to the H-cluster.

“This conformation has been suggested to be vital for efficient proton shuttling, but it had never been observed structurally. Coincidently, the cyanide binding helped us to capture such a transient state,” says Jifu Duan.

“These findings are important for researchers to understand the coupling of electron and proton transport which is not only relevant for H2-generating enzymes, but many additional biocatalysts,” concludes Thomas Happe.

More information: Jifu Duan et al, Cyanide Binding to [FeFe]‐Hydrogenase Stabilizes the Alternative Configuration of the Proton Transfer Pathway, Angewandte Chemie International Edition (2022). DOI: 10.1002/anie.202216903

Journal information: Angewandte Chemie International Edition  Angewandte Chemie 

Provided by Ruhr-Universitaet-Bochum 

A deep red, cranberry-tinted lipstick that’s also antimicrobial

A deep red, cranberry-tinted lipstick that's also antimicrobial
Adding cranberry extract to a lipstick cream allowed it to fight off viruses, bacteria and a type of fungus. Credit: ACS Applied Materials & Interfaces (2022). DOI: 10.1021/acsami.2c19460

Lipstick can be a confidence booster, enhance a costume and keep lips from chapping. But sharing a tube with a friend or family member can also spread infections. To develop a version with antimicrobial properties, researchers reporting in ACS Applied Materials & Interfaces have added cranberry extract to the formulation. Their deep red cream quickly inactivates disease-causing viruses, bacteria and a fungus that come in contact with it.

According to historians, people in ancient Egypt were the first to use make-up, applying pastes made from minerals and other substances in their environment. The formulations have evolved over the centuries, but now researchers have come full circle, looking again toward natural ingredients.

For example, recent studies have reported that lipstick formulas incorporating natural colorants, such as red dragon fruit, can result in products with both vibrant colors and antimicrobial activity. And previously, cranberry extract has been shown to inactivate viruses, bacteria and fungi. So, Ángel Serrano-Aroca and colleagues wanted to use cranberry extract to create a deep red lip tint with antimicrobial properties.

The research team mixed cranberry extract into a lipstick cream base, which contained shea butter, vitamin E, provitamin B5, babassu oil and avocado oil. In experiments, the reddened cream was added to cultures containing different viruses, bacteria and one fungal species. Both enveloped and non-enveloped virus types were completely inactivated within a minute of contact with the cranberry-containing cream.

And the multidrug-resistant bacteria, mycobacteria and fungus were substantially inactivated within five hours of applying the cream. The researchers suggest that their novel lipstick formula could offer protection against a variety of disease-causing microorganisms.

More information: Alberto Tuñón-Molina et al, Antimicrobial Lipstick: Bio-Based Composition against Viruses, Bacteria, and Fungi, ACS Applied Materials & Interfaces (2022). DOI: 10.1021/acsami.2c19460

Journal information: ACS Applied Materials and Interfaces 

Provided by American Chemical Society 

Using quantum-inspired computing to discover an improved catalyst for clean hydrogen

Using quantum-inspired computing, University of Toronto Engineering and Fujitsu discover improved catalyst for clean hydrogen
Graphical abstract. Credit: Matter (2022). DOI: 10.1016/j.matt.2022.11.031

Researchers from the University of Toronto’s Faculty of Applied Science & Engineering and Fujitsu have developed a new way of searching through ‘chemical space’ for materials with desirable properties.

The technique has resulted in a promising new catalyst material that could help lower the cost of producing clean hydrogen.

The discovery represents an important step toward more sustainable ways of storing energy, including from renewable but intermittent sources, such as solar and wind power.

“Scaling up the production of what we call green hydrogen is a priority for researchers around the world because it offers a carbon-free way to store electricity from any source,” says Ted Sargent, a professor in the Edward S. Rogers Sr. department of electrical and computer engineering and senior author on a new paper published in Matter.

“This work provides proof-of-concept for a new approach to overcoming one of the key remaining challenges, which is the lack of highly active catalyst materials to speed up the critical reactions.”

Today, nearly all commercial hydrogen is produced from natural gas. The process produces carbon dioxide as a byproduct: if the CO2 is vented to the atmosphere, the product is known as ‘grey hydrogen,’ but if the CO2 is captured and stored, it is called ‘blue hydrogen.’

By contrast, ‘green hydrogen’ is a carbon-free method that uses a device known as an electrolyzer to split water into hydrogen and oxygen gas. The hydrogen can later be burned or reacted in a fuel cell to regenerate the electricity. However, the low efficiency of available electrolyzers means that most of the energy in the water-splitting step is wasted as heat, rather than being captured in the hydrogen.

Researchers around the world are racing to find better catalyst materials that can improve this efficiency. But because each potential catalyst material can be made of several different chemical elements, combined in a variety of ways, the number of possible permutations quickly becomes overwhelming.

“One way to do it is by human intuition, by researching what materials other groups have made and trying something similar, but that’s pretty slow,” says department of materials science and engineering Ph.D. candidate Jehad Abed, one of two co-lead authors on the new paper.

“Another way is to use a computer model to simulate the chemical properties of all the potential materials we might try, starting from first principles. But in this case, the calculations get really complex, and the computational power needed to run the model becomes enormous.”

To find a way through, the team turned to the emerging field of quantum-inspired computing. They made use of the Digital Annealer, a tool that was created as the result of a long-standing collaboration between U of T Engineering and Fujitsu Research. This collaboration has also resulted in the creation of the Fujitsu Co-Creation Research Laboratory at the University of Toronto.

“The Digital Annealer is a hybrid of unique hardware and software designed to be highly efficient at solving combinatorial optimization problems,” says Hidetoshi Matsumura, senior researcher at Fujitsu Consulting (Canada) Inc.

“These problems include finding the most efficient route between multiple locations across a transportation network, or selecting a set of stocks to make up a balanced portfolio. Searching through different combinations of chemical elements to a find a catalyst with desired properties is another example, and it was a perfect challenge for our Digital Annealer to address.”

In the paper, the researchers used a technique called cluster expansion to analyze a truly enormous number of potential catalyst material designs—they estimate the total as a number on the order of hundreds of quadrillions. For perspective, one quadrillion is approximately the number of seconds that would pass by in 32 million years.

The results pointed toward a promising family of materials composed of ruthenium, chromium, manganese, antimony and oxygen, which had not been previously explored by other research groups.

The team synthesized several of these compounds and found that the best of them demonstrated a mass activity— a measure of the number of reactions that can be catalyzed per mass of the catalyst—that was approximately eight times higher than some of the best catalysts currently available.

The new catalyst has other advantages too: it operates well in acidic conditions, which is a requirement of state-of-the-art electrolyzer designs. Currently, these electrolyzers depend on catalysts made largely of iridium, which is a rare element that is costly to obtain. In comparison, ruthenium, the main component of the new catalyst, is more abundant and has a lower market price.

There is more work ahead for the team: for example, they aim to further optimize the stability of the new catalyst before it can be tested in an electrolyzer. Still, the latest work serves as a demonstration of the effectiveness of the new approach to searching chemical space.

“I think what’s exciting about this project is that it shows how you can solve really complex and important problems by combining expertise from different fields,” says electrical and computer engineering Ph.D. candidate Hitarth Choubisa, the other co-lead author of the paper.

“For a long time, materials scientists have been looking for these more efficient catalysts, and computational scientists have been designing more efficient algorithms, but the two efforts have been disconnected. When we brought them together, we were able to find a promising solution very quickly. I think there are a lot more useful discoveries to be made this way.”

More information: Hitarth Choubisa et al, Accelerated chemical space search using a quantum-inspired cluster expansion approach, Matter (2022). DOI: 10.1016/j.matt.2022.11.031

Journal information: Matter 

Provided by University of Toronto 

A pressure-sensitive device capable of characterizing gases using structural colors

Imaging gases in rainbow colors
Mechanism behind the multi-color imaging of a gas injected into the device. Top (top row) and cross-sectional (middle and bottom rows) views of the device and a gas flowing through it. Credit: Kota ShibaNational Institute for Materials Science

NIMS, Harvard University and the University of Connecticut have designed and fabricated a simple device capable of imaging a gas injected into it in multiple colors in accordance with its gaseous properties, enabling chromatic discrimination of different gases. This user-friendly device converts the pressure generated by an injected gas into structural colors, thereby imaging it. This technology may potentially have a wide range of applications, such as environmental monitoring, safety assurance and health care.

Imaging of gases is important in many gas-related basic and applied research projects as almost all ambient gases are colorless and invisible. Only a few methods for imaging ambient gas flow have been developed (e.g., the use of infrared cameras capable of detecting temperature changes and airflow measurements by means of releasing tracer particles into the air).

These methods require elaborate equipment and are unsuitable for imaging different types of gases in a consistent manner. In addition, the images they produce are unfit for the analysis of gaseous characteristics. A simple method capable of imaging and analyzing all types of gases may have a wide variety of applications, such as image-based measurements.

This research team recently fabricated a device capable of imaging and differentiating various gases using a wide range of colors (i.e., structural colors) through a simple procedure: polydimethylsiloxane (PDMS)—a soft material—was first shaped into a slab. Part of the PDMS surface was then treated with argon plasma. The plasma-treated PDMS slab was placed on the surface of a glass substrate with its plasma-treated surface down, and they came into complete contact.

The plasma-treated PDMS surface forms a periodic ripple-like micropattern when compressed by an injected gas passing through the tight boundary between the PDMS and glass layers. This compression and resultant micropattern formation lead to the production of structural colors. This mechanism is applicable to the imaging and differentiation of any type of gas. When the incoming gas flow is discontinued, structural colors disappear completely.

The degree of PDMS deformation depends on the flow rates, viscosities and densities of injected gases. As all gases have unique viscosities and densities, this device can be used to differentiate and analyze gas samples based on these properties under a constant flow rate.

In future research, the team will work to optimize the device by improving its sensitivity with the goal of making it compatible with various applications (e.g., identification of ambient gases and biological samples). The team will also consider developing a new gas identification technique by combining it with image recognition and machine learning techniques and fabricating a small, CCD (charge coupled device)-integrated device with a simple structure.

The study is published in the journal Advanced Science.

More information: Kota Shiba et al, Visualization of Flow‐Induced Strain Using Structural Color in Channel‐Free Polydimethylsiloxane Devices, Advanced Science (2022). DOI: 10.1002/advs.202204310

Journal information: Advanced Science 

Provided by National Institute for Materials Science 

Team creates protein-based material that can stop supersonic impacts

Creating a material that can stop supersonic impacts
The design concept of TSAM. a. Cartoon representation of the protein talin, F = FERM domain, R = rod domain, DD = dimerisation domain. The R1-R3 region is shown in orange. b. The control monovalent crosslinker 1 and the trivalent crosslinker 2, c. pGEL in the folded state, green boxes = flexible linkers, blue box = R1-R3 domains of talin. d. Resulting gelation for each crosslinker. e. Representation of the three-armed network structure formed from crosslinker 2 with no applied strain. f. pGEL in fully folded state presents length of ≈15 nm. g. When exposed to strain pGEL unfolds into a linear string of helices extending to ~65 nm in length. h. When exposed to higher strain, pGEL unfolds fully into extended polypeptide, increasing to a length of ~156 nm. Complete refolding can occur once strain is removed. i. Representation of the three-armed network structure with applied strain, causing extension of protein into opened helices form, increasing fibre length. Credit: bioRxiv (2022). DOI: 10.1101/2022.11.29.518433

A University of Kent team, led by Professors Ben Goult and Jen Hiscock, has created and patented a new shock-absorbing material that could revolutionize both the defense and planetary science sectors.

This novel protein-based family of materials, named TSAM (Talin Shock Absorbing Materials), represents the first known example of a SynBio (or synthetic biology) material capable of absorbing supersonic projectile impacts. This opens the door for the development of next-generation bulletproof armor and projectile capture materials to enable the study of hypervelocity impacts in space and the upper atmosphere (astrophysics).

Professor Ben Goult explained, “Our work on the protein talin, which is the cell’s natural shock absorber, has shown that this molecule contains a series of binary switch domains which open under tension and refold again once tension drops. This response to force gives talin its molecular shock absorbing properties, protecting our cells from the effects of large force changes. When we polymerized talin into a TSAM, we found the shock absorbing properties of talin monomers imparted the material with incredible properties.”

The team went on to demonstrate the real-world application of TSAMs, subjecting this hydrogel material to 1.5 km/s supersonic impacts—a faster velocity than particles in space impact both natural and man-made objects (typically > 1 km/s) and muzzle velocities from firearms—which commonly fall between 0.4–1.0 km/s. Furthermore, the team discovered that TSAMs can not only absorb the impact of basalt particles (~60 µM in diameter) and larger pieces of aluminum shrapnel, but also preserve these projectiles post-impact.

Current body armor tends to consist of a ceramic face backed by a fiber-reinforced composite, which is heavy and cumbersome. Also, while this armor is effective in blocking bullets and shrapnel, it doesn’t block the kinetic energy which can result in behind armor blunt trauma.

Furthermore, this form of armor is often irreversibly damaged after impact, because of compromised structural integrity preventing further use. This makes the incorporation of TSAMs into new armor designs a potential alternative to these traditional technologies, providing a lighter, longer-lasting armor that also protects the wearer against a wider range of injuries including those caused by shock.

In addition, the ability of TSAMs to both capture and preserve projectiles post-impact makes it applicable within the aerospace sector, where there is a need for energy dissipating materials to enable the effective collection of space debris, space dust and micrometeoroids for further scientific study.

Furthermore, these captured projectiles facilitate aerospace equipment design, improving the safety of astronauts and the longevity of costly aerospace equipment. Here TSAMs could provide an alternative to industry standard aerogels—which are liable to melt due to temperature elevation resulting from projectile impact.

Professor Jen Hiscock said, “This project arose from an interdisciplinary collaboration between fundamental biology, chemistry and materials science which has resulted in the production of this amazing new class of materials. We are very excited about the potential translational possibilities of TSAMs to solve real world problems. This is something that we are actively undertaking research into with the support of new collaborators within the defense and aerospace sectors.”

The work is published on the bioRxiv preprint server.

More information: Jack A. Doolan et al, Next generation protein-based materials capture and preserve projectiles from supersonic impacts, bioRxiv (2022). DOI: 10.1101/2022.11.29.518433

Provided by University of Kent 

Using machine learning to improve the toxicity assessment of chemicals

Using machine learning to improve the toxicity assessment of chemicals
Credit: University of Amsterdam

Researchers of the University of Amsterdam, together with colleagues at the University of Queensland and the Norwegian Institute for Water Research, have developed a strategy using machine learning to assess the toxicity of chemicals.

They present their approach in an article in Environmental Science & Technology for the special issue “Data Science for Advancing Environmental Science, Engineering, and Technology.” The models developed in this study can lead to substantial improvements when compared to conventional “in silico” assessments based on Quantitative Structure-Activity Relationship (QSAR) modeling.

According to the researchers, the use of machine learning can vastly improve the hazard assessment of molecules, both in the safe-by-design development of new chemicals and in the evaluation of existing chemicals. The importance of the latter is illustrated by the fact that European and U.S. chemical agencies have listed approximately 800,000 chemicals that have been developed over the years but for which there is little to no knowledge about environmental fate or toxicity.

Since an experimental assessment of chemical fate and toxicity requires much time, effort, and resources, modeling approaches are already used to predict hazard indicators. In particular the Quantitative Structure-Activity Relationship (QSAR) modeling is often applied, relating molecular features such as atomic arrangement and 3D structure to physicochemical properties and biological activity.

Based on the modeling results (or measured data where available), experts classify a molecule into categories as defined for example in the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). For specific categories, molecules are then subjected to more research, more active monitoring and eventually legislation.

However, this process has inherent drawbacks, much of which can be traced back to the limitations of the QSAR models. They are often based on very homogeneous training sets and assume a linear structure-activity relationship for making extrapolations. As a result, many chemicals are not well-represented by existing QSAR models and their uses can potentially lead to substantial prediction errors and misclassification of chemicals.

Using machine learning to improve the toxicity assessment of chemicals
Overall workflow of the study, from the raw data to the finally generated models. Image taken from the ES&T paper. Credit: University of Amsterdam

Skipping the QSAR prediction

In their paper published in Environmental Science & Technology, Dr. Saer Samanipour and co-authors propose an alternative evaluation strategy that skips the QSAR prediction step altogether.

Samanipour, an environmental analytical scientist at the University of Amsterdam’s Van ‘t Hoff Institute for Molecular Sciences teamed up with Dr. Antonia Praetorius, an environmental chemist at the Institute for Biodiversity and Ecosystem Dynamics of the same university. Together with colleagues at the University of Queensland and the Norwegian Institute for Water Research, they developed a machine learning-based strategy for the direct classification of acute aquatic toxicity of chemicals based on molecular descriptors.

The model was developed and tested via 907 experimentally obtained data for acute fish toxicity (96h LC50 values). The new model skips the explicit prediction of a toxicity value (96h LC50) for each chemical, but directly classifies each chemical into a number of pre-defined toxicity categories.

These categories can for example be defined by specific regulations or standardization systems, as demonstrated in the article with the GHS categories for acute aquatic hazard. The model explained around 90% of the variance in the data used in the training set and around 80% for the test set data.

Higher accuracy predictions

This direct classification strategy resulted in a fivefold decrease in the incorrect categorization compared to a strategy based on a QSAR regression model. Subsequently, the researchers expanded their strategy to predict the toxicity categories of a large set of 32,000 chemicals.

They demonstrate that their direct classification approach results in higher accuracy predictions because experimental datasets from different sources and for different chemical families can be grouped to generate larger training sets. It can be adapted to different predefined categories as prescribed by various international regulations and classification or labeling systems.

In the future, the direct classification approach can also be expanded to other hazard categories (e.g. chronic toxicity) as well as to environmental fate (e.g. mobility or persistence) and shows great potential for improving in-silico tools for chemical hazard and risk assessment.

More information: Saer Samanipour et al, From Molecular Descriptors to Intrinsic Fish Toxicity of Chemicals: An Alternative Approach to Chemical Prioritization, Environmental Science & Technology (2022). DOI: 10.1021/acs.est.2c07353

Journal information: Environmental Science & Technology 

Provided by University of Amsterdam 

Using plant-derived nanothylakoid units to induce anabolism in mammals to reduce disease progression

Using plant derived nanothylakoid units to induce anabolism in mammals to reduce disease progression
Preparation and characterization of CM-NTUs. a, Diameters of thylakoid (TK) organelles and NTUs. b, Cryo-TEM images of thylakoid organelles and NTUs. c, Schematic illustration of photosynthesis light reaction-associated proteins and the photosynthetic electron transport chain in NTUs. FD, ferredoxin; PC, plastocyanin; PSI, photosystem I; PSII, photosystem II; PQ, plastoquinone. d, Proteomics analysis of NTUs. The identified proteins were classified according to their cellular components and biological processes and analyzed using protein analysis through evolutionary relationships (PANTHER) overrepresentation test with Fisher’s exact test for significance. e, ATP and NADPH production capacity of NTUs in vitro (n = 3, mean ± s.d.). f, Immunodetection of D1 and D2 abundance in NTUs under light illumination for 0–32 h (80 µmol photons m−2 s−1) or darkness for 0–7 days (at room temperature). Similar results were obtained from three biologically independent samples. g,h, ATP production of NTUs was measured under light illumination (g) for 0–32 h (80 µmol photons m−2 s−1) or in the dark (h) for 0–7 days (at room temperature) (n = 3, mean ± s.d.). i, Proteomics analysis of CM. The identified proteins were classified according to their cellular components. j, Content and categories of proteins in the CM involved in vesicle targeting and membrane fusion. k, Western blot analysis of Na+/K+-ATPase and β-tubulin in CM and cytoplasm. Na+/K+-ATPase was significantly enriched, and β-tubulin was present at low levels on the CM. l, Diameters of NTUs, CM, LNP-NTUs and CM-NTUs. m, Zeta potential of NTUs, CM, LNP-NTUs and CM-NTUs (n = 3, mean ± s.d.). n, Cryo-TEM images of LNPs, LNP-NTUs, CM and CM-NTUs. n represents the number of biologically independent samples. P values are indicated on the graph and were determined using two-tailed t-test (e). Scale bars, 50 nm (n) or 100 nm (b). Credit: Nature (2022). DOI: 10.1038/s41586-022-05499-y

A team of researchers at Zhejiang University School of Medicine has developed a way to use photosynthetic cells from plants when treating osteoarthritis in mice.

In their paper published in the journal Nature, the group describes how they created nanoscale thylakoid structures, called nanothylakoid units, in plants and delivered them into animal cells as a way to slow or stop disease progression. Two of the team members, Pengfei Chen and Xianfeng Lin have also published a Research Briefing outlining their work in the same journal issue.

Prior research has shown that in some progressive diseases, such as osteoarthritis, cells lack the amount of energy they need to function properly due to insufficient anabolism (where simple molecules are converted to complex molecules). Prior research has also shown that the compound ATP provides the energy needed by mammalian cells.

Prior research has also shown that the molecule NADPH plays an important role in allowing cells to use ATP. And finally, prior research has also shown that both ATP and NADHP are produced in plants during photosynthesis. The researchers therefore wondered if it might be possible to deliver some of the plant machinery into a mammalian cell where it could be used to produce ATP and NADPH for use by the mammalian cells when a light was applied, instigating the photosynthetic process.

To find out, the researchers created structures called nanothylakoid units (NTUs) from plant chloroplasts. They then covered them with mouse cells to prevent the mouse immune system from attacking when the NTUs were injected into the knee joints of mice with osteoarthritis.

Next, they shined a light on the joints to incite the photosynthetic process and thus the production of ATP and NADPH. Testing showed that the technique led to improved anabolism in the mouse cells, which in turn led to reducing the progression of the disease (slowed cartilage degeneration) in the test mice.

The researchers suggest their initial experiments show that their approach holds promise as a therapeutic approach to treating progressive diseases. They also note that the same approach could be used to metabolize cells as part of a process to create biofuels and perhaps other useful chemicals.

More information: Pengfei Chen et al, A plant-derived natural photosynthetic system for improving cell anabolism, Nature (2022). DOI: 10.1038/s41586-022-05499-y

Plant-cell machinery for making metabolites transferred to mammalian cells, Nature (2022). DOI: 10.1038/d41586-022-03629-0

Journal information: Nature 

© 2022 Science X Network

How two key proteins orchestrate flip-flopping cholesterol in the cell membrane

Flip-flopping cholesterol in the cell membrane
Cholesterol transporter protein ABCA1 at the plasma membrane, and cholesterol transfer protein Aster-A at the endoplasmic reticulum membrane, function cooperatively to keep the amount of cholesterol (cargo) in the inner plasma membrane low. Credit: Mindy Takamiya/Kyoto University iCeMS

Cholesterol is an essential component of the membrane surrounding every human cell, despite its poor reputation as a health concern when its blood levels are too high. The key to health is having the right amount of cholesterol in the right places. Maintaining appropriate levels is known as cholesterol homeostasis.

Researchers at the Institute for Integrated Cell-Material Science (iCeMS) at Kyoto University in Japan have gained new insights into how cells achieve cholesterol homeostasis within the cell membrane. The findings are published in the Journal of Biological Chemistry.

Cholesterol molecules are packed inside the cell membrane at levels that control membrane fluidity, thickness and flexibility. These characteristics are vital for making the membrane a selective semi-permeable barrier, with crucial control over what substances can travel into and out of cells.

“Disturbances in cholesterol homeostasis can lead to some serious diseases, but it has been unclear how cells detect and respond to changes in cholesterol levels in the cell membrane,” says iCeMS cellular biochemist Kazumitsu Ueda.

Ueda and his colleague Fumihiko Ogasawara have now revealed a vital role of two proteins in maintaining an appropriate distribution of cholesterol inside cells and their membranes.

The first protein, called ATP-binding cassette A1 (ABCA1) translocates cholesterol within the membrane. The cell membrane is composed of a lipid bilayer, with inner and outer layers of fatty molecules (phospholipids, cholesterol, and glycolipids) oriented in opposite directions.

A key new insight reported in this current study is that the ABCA1 protein controls the transfer of cholesterol molecules from the inner layer to the outer layer. The researchers call this process “cholesterol flopping.” Their previous work explored this protein’s role in facilitating cholesterol transfer through the bloodstream in the form of high-density lipoprotein (HDL), sometimes called good cholesterol.

Ueda and Ogasawara also uncovered details of how a second protein—cholesterol transfer protein Aster-A—acts cooperatively with ABCA1 to maintain the crucial asymmetric distribution of cholesterol, with more cholesterol in the outer layer of the cell membrane than the inner. Aster-A is located inside the cell embedded in the endoplasmic reticulum. When there is an increase in the cholesterol level in the inner layer of the cell membrane, Aster-A forms a bridge transferring cholesterol from the cell membrane to the endoplasmic reticulum.

The researchers describe how the asymmetric distribution of cholesterol in the membrane allows it to serve a signaling function, influencing other cellular processes in ways that depend on the degree of asymmetry. They suggest that this explains why defects in the normal functioning of ABCA1 can cause faulty molecular signaling that may lead to cancer and autoimmune diseases.

“The progress we have made needs to be built on to better understand all the implications of these cholesterol homeostasis processes in both health and disease,” Ueda concludes. He hopes this may eventually open new avenues to treating diseases linked to cholesterol imbalance.

More information: Fumihiko Ogasawara et al, ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane, Journal of Biological Chemistry (2022). DOI: 10.1016/j.jbc.2022.102702

Journal information: Journal of Biological Chemistry 

Provided by Kyoto University 

Recycled gold from SIM cards could help make drugs more sustainable

Recycled gold from SIM cards could help make drugs more sustainable
Graphical abstract. Credit: ACS Sustainable Chemistry & Engineering (2022). DOI: 10.1021/acssuschemeng.2c04092

Re-using gold from electronic waste prevents it from being lost to landfill, and using this reclaimed gold for drug manufacture reduces the need to mine new materials. Current catalysts are often made of rare metals, which are extracted using expensive, energy-intensive and damaging mining processes.

The method for extracting gold was developed by researchers at the University of Cagliari in Italy and the process for using the recovered gold was developed by researchers at Imperial College London. The study is published in ACS Sustainable Chemistry & Engineering.

Waste electrical and electronic equipment (WEEE) is typically sent to landfill, as separating and extracting the components requires a lot of energy and harsh chemicals, undermining its economic viability. However, WEEE contains a wealth of metals that could be used in a range of new products.

Finding ways to recover and use these metals in a low-cost, low-energy and non-toxic way is therefore crucial for making our use of electronic goods more sustainable.

Lead researcher Professor James Wilton-Ely, from the Department of Chemistry at Imperial, said, “It is shocking that most of our electronic waste goes to landfill and this is the opposite of what we should be doing to curate our precious elemental resources. Our approach aims to reduce the waste already within our communities and make it a valuable resource for new catalysts, thereby also reducing our dependence on environmentally damaging mining practices.”

“We are currently paying to get rid of electronic waste, but processes like ours can help reframe this ‘waste’ as a resource. Even SIM cards, which we routinely discard, have a value and can be used to reduce reliance on mining and this approach has the potential to improve the sustainability of processes such as drug manufacture.”

Professors Angela Serpe and Paola Deplano, from the University of Cagliari, developed a low-cost way to extract gold and other valued metals from electronic waste such as printed circuit boards (PCBs), SIM cards and printer cartridges under mild conditions. This patented process involves selective steps for the sustainable leaching and recovery of base metals like nickel, then copper, silver and, finally, gold, using green and safe reagents.

However, the gold produced from this process is part of a molecular compound and so cannot be re-used again for electronics without investing a lot more energy to obtain the gold metal. Seeking a use for this compound of recovered gold, the team of Professor Wilton-Ely and his colleague, Professor Chris Braddock, investigated whether it could be applied as a catalyst in the manufacture of useful compounds, including pharmaceutical intermediates.

Catalysts are used to increase the rate of a chemical reaction while remaining unchanged and are used in most processes to produce materials. The team tested the gold compound in a number of reactions commonly used in pharmaceutical manufacture, for example for making anti-inflammatory and pain-relief drugs.

They found that the gold compound performed as well, or better, than the currently used catalysts, and is also reusable, further improving its sustainability.

The researchers suggest that making it economically viable to recover gold from electronic waste could create spin-off uses for other components recovered in the process. For example, in the process, copper and nickel are also separated out, as is the plastic itself, with all these components potentially being used in new products.

Sean McCarthy, the Ph.D. student leading the research in the lab at Imperial, said, “By weight, a computer contains far more precious metals than mined ore, providing a concentrated source of these metals in an ‘urban mine’.”

Professor Serpe said, “Research like ours aims to contribute to the cost-effective and sustainable recovery of metals by building a bridge between the supply of precious metals from scrap and industrial demand, bypassing the use of virgin raw materials.”

The teams are working to extend this approach to the recovery and re-use of the palladium content of end-of-life automotive catalytic converters. This is particularly pressing as palladium is widely used in catalysis and is even more expensive than gold.

More information: Sean McCarthy et al, Homogeneous Gold Catalysis Using Complexes Recovered from Waste Electronic Equipment, ACS Sustainable Chemistry & Engineering (2022). DOI: 10.1021/acssuschemeng.2c04092

Provided by Imperial College London 

Microbial miners could help humans colonize the moon and Mars

Microbial miners could help humans colonize the moon and Mars
David Kisailus, UCI professor of materials science and engineering, holds a model of crystal magnetite. He and his fellow researchers found that microbes living in Chile’s Atacama Desert transform magnetite to a different iron oxide phase called hematite in the process of acquiring the iron that’s necessary for their survival in a harsh environment. Credit: Steve Zylius / UCI

The biochemical process by which cyanobacteria acquire nutrients from rocks in Chile’s Atacama Desert has inspired engineers at the University of California, Irvine to think of new ways microbes might help humans build colonies on the moon and Mars.

Researchers in UCI’s Department of Materials Science and Engineering and Johns Hopkins University’s Department of Biology used high-resolution electron microscopy and advanced spectroscopic imaging techniques to gain a precise understanding of how microorganisms modify both naturally occurring minerals and synthetically made nanoceramics. A key factor, according to the scientists, is that cyanobacteria produce biofilms that dissolve magnetic iron oxide particles within gypsum rocks, subsequently transforming the magnetite into oxidized hematite.

The team’s findings, which are the subject of a paper published recently in the journal Materials Today Bio, could provide a pathway for new biomimetic mining methods. The authors also said they see the results as a step toward using microorganisms in large-scale 3D printing or additive manufacturing at a scale that’s useful in civil engineering in harsh environments, like those on the moon and Mars.

“Through a biological process that has evolved over millions of years, these tiny miners excavate rocks, extracting the minerals that are essential to the physiological functions, such as photosynthesis, that enable their survival,” said corresponding author David Kisailus, UCI professor of materials science and engineering. “Could humans use a similar biochemical approach to obtain and manipulate the minerals that we find valuable? This project has led us down that pathway.”

The Atacama Desert is one of the driest and most inhospitable places on Earth, but Chroococcidiopsis, a cyanobacterium found in gypsum samples collected there by the Johns Hopkins team, has developed “the most amazing adaptations to survive its rocky habitat,” said co-author Jocelyne DiRuggiero, associate professor of biology at the Baltimore university.

“Some of those traits include producing chlorophyll that absorbs far-red photons and the ability to extract water and iron from surrounding minerals,” she added.

Using advanced electron microscopes and spectroscopic instruments, the researchers found evidence of the microbes in the gypsum by observing how the very minerals contained within were transformed.

“Cyanobacteria cells promoted magnetite dissolution and iron solubilization by producing abundant extracellular polymeric substances, leading to the dissolution and oxidation of magnetite to hematite,” DiRuggiero said. “Production of siderophores [iron-binding compounds generated by bacteria and fungi] was enhanced in the presence of magnetite nanoparticles, suggesting their use by the cyanobacteria to acquire iron from magnetite.”

Kisailus said the way the microorganisms process metals in their desolate home made him think about our own mining and manufacturing practices.

“When we mine for minerals, we often wind up with ores that may present challenges for extraction of valuable metals,” he said. “We frequently need to put these ores through extreme processing to transform it into something of value. That practice can be monetarily and environmentally costly.”

Kisailus said he is now pondering a biochemical approach using natural or synthetic analogs to siderophores, enzymes and other secretions to manipulate minerals where only a large mechanical crusher currently works. And taking a leap from here, he said there could also be a way to get microorganisms to employ similar biochemical capabilities to produce an engineered material on demand in less-than-convenient locations.

“I call it ‘lunar forming’ instead of terraforming,” Kisailus said. “If you want to build something on the moon, instead of going through the expense of having people do it, we could have robotic systems 3D-print media and then have the microbes reconfigure it into something of value. This could be done without endangering human lives.”

He added that humans don’t always need to use Edisonian approaches to figure out how to do things.

“This is the main theme of my Biomimetics and Nanostructured Materials Lab. Why try to reinvent the wheel when nature’s perfected it over hundreds of millions of years?” Kisailus said. “We just have to extract the secrets and blueprints for what nature does and apply or adapt them to what we need.”

More information: Wei Huang et al, Iron acquisition and mineral transformation by cyanobacteria living in extreme environments, Materials Today Bio (2022). DOI: 10.1016/j.mtbio.2022.100493

Provided by University of California, Irvine