Category: Chemistry

Around 500 million years ago, early vertebrates in the seas became fish, adopting an inner skeleton and a flexible spine based on a nanocomposite of fibers and mineral, known as bone material. This “invention” of evolution was so successful that the basic structure was also adopted for later vertebrates that lived on land.

However, while the bones of all terrestrial vertebrates are basically equipped with bone cells (osteocytes), certain fish species continued to evolve and finally managed to create a more energy efficient material: bone lacking bone cells, found today for example in fish such as salmon, medaka or tilapia.

Samples with and without bone cells

“We asked ourselves how bone samples with and without bone cells actually differ in their microstructures and properties,” says Prof. Paul Zaslansky, who heads a research group at Charité Berlin and specializes in mineralized biomaterials including teeth and bones.

Together with Ph.D. student Andreia Silvera and international partners, they have now compared bone samples from zebrafish and medaka. Both fish species are of similar size and live in similar conditions, so their skeletons must withstand similar stresses. However, while zebrafish have bone cells, the skeleton of medaka do not.

“The background to the question is that the function of bone cells in bone and how they change with age is of great interest to the aging population,” Silvera explains. Bone cells can respond to physical stress by sending biochemical signals that lead to the formation or resorption of bone tissue, adapting to load. But with age or in diseases such as osteoporosis, this mechanism no longer seems to work.

“With our basic research, we want to find out how bones with and without bone cells differ and cope with the challenges of external stress,” Zaslansky says.

Strength and elasticity

Bones have a complex structure: they comprise nanofibers of collagen and nanoparticles of mineral but also other minor ingredients. Certain protein compounds, so called Proteoglycans (PGs), are embedded in a tissue of collagen fibers and nanocrystals and play important roles in tissue formation and maintenance.

“PGs may be compared to salt in the soup. Too little or too much of it is not good,” Zaslansky says. The PGs can retain water, and there are plenty of PGs in healthy cartilage, making it as elastic as a sponge. Together, these components form an extracellular matrix (ECM), a 3D structure that provides strength and elasticity, ensuring function for many years.

In bones, an open network (Lacunar Channel Network or LCN) of channels and pores with diameters ranging from a few hundred nanometers to micrometers is created in this 3D structure. This LCN hosts the bone osteocytes, cells that sense load and orchestrate bone remodeling. In the LCN and within the nanocomposite, bone contains up to 20% of its volume in water, with many functions including toughening and adaptation to mechanical stress.

Neutron tomography at BER II

To determine the amount of incorporated water, the researchers first immersed bone samples in water and transilluminated them with neutrons, provided by the Berlin experimental reactor BER II at HZB—followed by saturation in deuterated heavy water (D₂O). 3D data was collected again and the difference between the two bone states allowed the team to determine for each spine vertebrae the precise amount of water displaced by diffusion of the D₂O.

“In addition, we examined sections of the bone samples, analyzed them by electron microscopy and micro CT and we also determined the PG concentration with Raman spectroscopy,” Silvera explains.

Surprising results: PGs make the difference

Until now, it was assumed that both bone types contain similar amounts of water and had very similar composition and properties. In fact however, the neutron examination showed that the bone material of zebrafish releases half as much water as that of medaka. This is all the more surprising because these bones have a very similar microstructure of mineralized collagen fibers, but zebrafish also contain large cell spaces within the LCN.

“My first reaction was, ‘This must be wrong!’ So we checked everything thoroughly and realized it’s really revolutionary,” recalls Zaslansky. The only explanation for the difference is that the bone matrices of the two species differ in a fundamental compositional component that affects water permeability. And here, both histological studies and Raman spectroscopy show: it’s the small but important contribution of PGs. The medaka samples contain far less PG than the zebrafish samples.

“This is a new finding: although both fish cope with similar stresses, their bone materials do not have the same water permeability properties,” says Silveira.

The study is published in the journal Materials & Design.

“We hope these results will help us better understand bone diseases as well,” Zaslansky says. Why are some bones better at responding to stress than others? What happens when bones age? Could it be that they lose PGs, and become less watertight? Perhaps aging or pathology such as osteoporosis changes the bone that surrounds bone cells, which makes it difficult to remodel and form bone tissue that works correctly?

More information: Andreia Silveira et al, Water flow through bone: Neutron tomography reveals differences in water permeability between osteocytic and anosteocytic bone material, Materials & Design (2022). DOI: 10.1016/j.matdes.2022.111275

Provided by Helmholtz Association of German Research Centres 

Chemical reactions occur on the scale of atomic vibrations—one million times smaller than the thickness of a human hair. These tiny movements are difficult to control.

Established methods include the control of temperature or providing surfaces and complexes in solution made from rare materials. They tackle the problem on a larger scale and cannot target specific parts of the molecule. Ideally, researchers would like to provide only a small amount of energy to some atoms at the right time, just like a billiard player wants to nudge just one ball on the table.

In recent years, it became clear that molecules undergo fundamental changes when they are placed in optical cavities with opposing mirrors. Inside those confines, the system is forced to interact with virtual light, or photons. Crucially, this interaction changes the rate of chemical reactions—an effect that was observed in experiments but whose underlying mechanism remained a mystery.

Now a team of theoretical physicists from Germany, Sweden, Italy and the U.S.A. has come up with a possible explanation, which qualitatively agrees with the experimental results.

The team involved researchers from the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg, Germany, Chalmers University of Technology in Sweden, the Center for Computational Quantum Physics at the Flatiron Institute, Harvard University (both in the U.S.A.), and the Istituto per i Processi Chimico Fisici at the CNR (National Research Council) in Italy.

Using an advanced theoretical method, called Quantum-Electrodynamical Density-Functional Theory (QEDFT), the authors have unveiled the microscopic mechanism which reduces the chemical reaction rate, for the specific case of the deprotection reaction of 1-phenyl-2-trimethylsilylacetylene. Their findings are in agreement with the observations by the group of Thomas Ebbesen in Strasbourg.

The team discovered that the conditions inside the optical cavity affect the energy which makes the atoms vibrate around the molecule’s single bonds, which are critical for the chemical reaction.

Outside the cavity, that energy is usually deposited in a single bond during the reaction, which can ultimately break the bond—a key step in a chemical reaction. “However, we find that the cavity introduces a new pathway, so that the energy is less likely to be funneled only into a single bond,” says lead author Christian Schäfer. “This is the key process which inhibits the chemical reaction, because the probability to break a specific bond is diminished.”

Manipulating materials through the use of cavities (“polaritonic chemistry”) is a powerful tool with many potential applications, according to the paper’s author Enrico Ronca, who works at CNR: “For instance, it was observed that coupling to specific vibrational excitations can inhibit, steer, and even catalyze a chemical process at room temperature. Our theoretical work enhances the understanding of the underlying microscopic mechanisms for the specific case of a reaction inhibited by the field.”

While the authors point out that important aspects remain to be understood and further experimental validation is required, they also highlight the special role of this new direction.

“This works puts the controversial field of polaritonic chemistry onto a different level,” adds Angel Rubio, the Director of the MPSD’s Theory Department. “It provides fundamental insights into the microscopic mechanisms that enable the control of chemical reactions. We expect the present findings to be applicable to a larger set of relevant reactions (including click chemical reactions linked to this year’s Nobel Prize in chemistry) under strong light-matter coupling conditions.”

The paper is published in the journal Nature Communications.

More information: Christian Schäfer et al, Shining light on the microscopic resonant mechanism responsible for cavity-mediated chemical reactivity, Nature Communications (2022). DOI: 10.1038/s41467-022-35363-6

Journal information: Nature Communications 

Provided by Max Planck Society 

When it comes to kitchen spills, paper towels and rags do the job. But using a hydrogel—a gelatin-like material in the form of a dry sheet—researchers have crafted a better picker-upper that absorbs and holds about three times more water-based liquid. The method, presented on December 21 in the journal Matter, produces an absorbent, foldable, and cuttable “gel sheet” that may one day find use in our kitchens or operating rooms to soak up liquids.

There are generally two types of materials that absorb liquids—porous materials and hydrogels. Porous materials like cloth and paper are flexible, foldable, and easy to use, but not very absorbent. On the other hand, superabsorbent hydrogels that are made of polymer, a web of large molecules, can soak up more than 100 times their weight in water. However, when dried, these hydrogels become brittle solids that crumble.

“We reimagined what a hydrogel can look like,” says corresponding author Srinivasa Raghavan of the University of Maryland. “What we’ve done is combine the desired properties of a paper towel and a hydrogel.”

To craft the gel sheets, the research team first mixed in acid, base, and other ingredients for the hydrogel in a zip-top bag. Like vinegar meeting baking soda, the mixture released carbon dioxide bubbles within the gel, creating a porous and foam-like material. Next, the zip-top bag was sandwiched between glass slabs to form a sheet and then exposed to UV light, which sets the liquid around the bubbles, leaving pores behind. Lastly, the team dipped the set sheet in alcohol and glycerol and air-dried it. This enabled the dried gel sheet to remain soft and flexible, similar to a fabric’s texture.

“To our knowledge, this is the first hydrogel that has been reported to have such tactile and mechanical properties,” says Raghavan. The gel sheets also stayed soft and flexible in ambient conditions for a year, indicating stability. “We are trying to achieve some unique properties with simple starting materials.”

Compared to a commercial cloth pad and a paper towel, a gel sheet the same size can absorb more than three times the amount of liquid than others. When researchers placed the gel sheet over 25 mL (0.8 oz) of spilled water, the sheet swelled and soaked it up within 20 seconds, holding the water without dripping. However, the cloth pad only absorbed about 60% of the water, leaving drips behind.

The gel sheet also performed well with thick liquids, such as syrup, blood, and even fluids that are a million times thicker than water. The researchers found that the gel sheet could absorb nearly 40 mL (1.4 oz) of blood within 60 seconds, while gauze dressing soaked up only 55% of the blood. The gel sheet also holds its liquid well, whereas the blood-soaked gauze trickles. Compared to sanitary pads, sponges, and gauze, the gel sheet absorbed over two times more blood than the others.

“To our knowledge, this is the first hydrogel that has been reported to have such tactile and mechanical properties,” says Raghavan. The gel sheets also stayed soft and flexible in ambient conditions for a year, indicating stability. “We are trying to achieve some unique properties with simple starting materials.”

Compared to a commercial cloth pad and a paper towel, a gel sheet the same size can absorb more than three times the amount of liquid than others. When researchers placed the gel sheet over 25 mL (0.8 oz) of spilled water, the sheet swelled and soaked it up within 20 seconds, holding the water without dripping. However, the cloth pad only absorbed about 60% of the water, leaving drips behind.

The gel sheet also performed well with thick liquids, such as syrup, blood, and even fluids that are a million times thicker than water. The researchers found that the gel sheet could absorb nearly 40 mL (1.4 oz) of blood within 60 seconds, while gauze dressing soaked up only 55% of the blood. The gel sheet also holds its liquid well, whereas the blood-soaked gauze trickles. Compared to sanitary pads, sponges, and gauze, the gel sheet absorbed over two times more blood than the others.

Next, the team plans to optimize their gel sheets by increasing absorbency, strengthening the material, lowering the cost, and making the sheets reusable. The researchers are also looking to develop gel sheets for absorbing oil.

“In principle, the gel sheets could be a superior form of paper towels,” says Raghavan. He envisions the gel sheets picking up spills in kitchens and laboratories, as well as cleaning up blood from surgeries and menstrual bleeding. Because of their flexible and absorbent nature, gel sheets also have the potential to stop bleeding from severe wounds as dressing. “I’m always interested in taking our inventions further than just publishing a paper. It would be wonderful to take it to actual practical use.”

More information: Srinivasa R. Raghavan, A Better Picker-Upper: Superabsorbent Gel Sheets with Fabric-Like Flexibility, Matter (2022). DOI: 10.1016/j.matt.2022.11.021. www.cell.com/matter/fulltext/S2590-2385(22)00652-X

Journal information: Matter 

Provided by Cell Press 

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 

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 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 

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.

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 

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

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