. Scientific Frontline

Tuesday, October 17, 2023

Unlocking the secrets of cell behavior on soft substrates: A paradigm shift in mechanobiology

Figure showing cancer cells (Osteosarcoma cells) on a printed protein spot. Scale bar: 50 μm.
Photo Credit: Turku Bioscience Centre / James Conway and Hellyeh Hamid

A research group from the University of Turku and Turku Bioscience Centre together with Misvik Biology Ltd in Finland have develop a new method for studying how cancer cells function in softer and stiffer tissue environments. This insight challenges the existing paradigm, opening up new possibilities for research in cancer biology and tissue engineering.

A longstanding belief has been that cells outside the body prefer to spread and grow on stiffer surfaces. This is similar to when we walk on a concrete sidewalk (very stiff) and find it preferable to walking in mud (very soft). For this reason, cells, including stem cells, are continuously cultured on very stiff plastic or glass for research purposes. This idea also resonates with cancer cells thriving within a hard lump they form in tissues. Usually, the stiffer the tumor, the poorer the patients’ prognosis. However, the stiffness of the tissues in our body (e.g., bone versus brain) is not the same. In fact, some cells like neurons and fat cells grow and function effectively in very soft surroundings.

The research group from the University of Turku and Turku Bioscience Centre collaborated with Misvik Biology Ltd, a biotechnology company based in Turku, Finland, to understand how cells function in softer environments and how these could be better modelled outside the human body. They used computational modelling and a large array of growth conditions to meticulously compare cell behavior on soft and stiff surfaces at an unprecedented resolution.

New Cancer Therapy Target Stops Tumor Cells From Sharing Resources

When missing a critical signaling enzyme, liver cells (blue) use vesicles (green) to communicate and share resources in order to multiply. Cancer cells may use the same process to resist therapy.
Image Credit: Courtesy of University of California San Diego

The body has many molecular processes in place to help control cell proliferation, turning it on and off as necessary in different circumstances and in different organs. This is well-exemplified by the liver, which has a high capacity for regeneration to support its important detoxification and metabolic functions.

“Cells in the liver multiply more quickly and effectively than any other cells in the body, which makes the liver the ideal place to study the biological processes that control cell division,” said Feng. “These are the same processes that go awry in cancer, and so one promising approach to treating cancer is targeting cell proliferation.”

In previous research, Feng and his team observed that a minority of liver cells in mice could still proliferate even when the cells were genetically engineered to lack a critical signaling enzyme required for cell proliferation. This enzyme, called Shp2, helps liver cells know when it’s time to divide during liver regeneration. Shp2 is also a known target for treating various cancers, and Shp2 inhibitors are involved in several ongoing clinical trials.

Decontamination method zaps pollutants from soil

Yi Cheng (from left), James Tour and Bing Deng
Photo Credit: Gustavo Raskosky/Rice University

Filtration systems are designed to capture multiple harmful substances from water or air simultaneously, but pollutants in soil can only be tackled individually or a few at a time ⎯ at least for now.

A method developed by Rice University scientists and collaborators at the United States Army Engineer Research and Development Center (ERDC) could help turn soil remediation processes from piecemeal to wholesale.

A team of Rice scientists led by chemist James Tour and researchers from the geotechnical structures and environmental engineering branches of the ERDC showed that mixing polluted soil with nontoxic, carbon-rich compounds that propel electrical current, such as biochar, then zapping the mix with short bursts of electricity flushes out both organic pollutants and heavy metals without using water or generating waste.

Amitriptyline helps relieve IBS symptoms

Generic image of amitriptyline tablets

A cheap and widely available prescription drug can improve symptoms of irritable bowel syndrome in patients seen in GP surgeries, new research presented at UEG Week 2023 has found.

Amitriptyline, which is commonly used at low doses for a range of health concerns, has been found to improve irritable bowel syndrome (IBS) symptoms too, according to the results of the ATLANTIS trial.

Led by researchers at the Universities of Leeds, Bristol and Southampton, and funded by the National Institute for Health and Care Research (NIHR), the study was conducted in primary care. GPs prescribed the drug and patients managed their own dose based on the severity of their symptoms, using an adjustment document designed for the trial. Most people with IBS are seen and managed in primary care by their GP, which means that the results of this trial are likely to be applicable to many people with the condition.

The results showed that patients taking amitriptyline were almost twice as likely to report an overall improvement in symptoms as those taking a placebo.

Now the trial team is recommending that GPs support their patients with IBS to use amitriptyline to manage their symptoms – and has made the dose adjustment document available for clinicians and patients.

Boosting weak immune system: scientists find an unusual weapon against virus

An overview of how the method proposed by the Sieweke group boosts weak immune system. (A) M-CSF cytokine works in the bone marrow to promote generation of monocytes and macrophages, without disturbing the formation of other immune cells; (B) Monocytes and macrophages activate natural killer cells to enable them to target virus-infected cells and kill them through cell–cell contact and the release of toxic agents.
Illustration Credit: © EMBO
(CC BY 4.0 DEED)

Infections with cytomegalovirus (CMV) are extremely common and often pose no major threat to the vast majority of people. They can, however, be deadly for people whose immune system is weakened, e.g., after bone marrow transplantation. Current treatments against CMV infections are very limited and can have severe side effects. Researchers led by Prof. Michael Sieweke at the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology and the Center of Immunology of Marseille Luminy (CIML) propose a new way to protect against CMV. Instead of targeting the virus, their approach boosts the weak immune system and lets it fight the virus on its own. The results were published in the journal EMBO Molecular Medicine.

Some viruses can be dormant throughout a person’s life and cause no harm but become dangerous when the immune system is weakened. One such virus is human cytomegalovirus (CMV). Harmless to the general public but life-threatening to patients with a suppressed immune system.

How to help save plants from extinction

California lilac, a species whose critical limits were obtained for this project
Photo Credit: Karen Udy Chang/Wikimedia Commons

Now is the time to identify the conditions that cause plants to die. Doing so will allow us to better protect plants by choosing conservation targets more strategically, UC Riverside botanists argue in a new paper. 

Published in the Oxford Academic journal Conservation Physiology, the paper demonstrates how scientists can learn the limits past which plants’ vital functions shut down, and makes the case that not doing so is a mistake in this era of increasing drought and wildfires.

“We can measure the amount of water loss plants can tolerate before they start to wilt, and we can learn the temperature at which photosynthesis stops for different kinds of plants,” said Louis Santiago, UCR botany professor and corresponding author of the paper. 

“It is so important to measure the critical limits of when things will fail, and not just how they’re doing now,” he said.

The UCR team believes understanding the current physiological status of a plant species during stress — which so many are experiencing more often with hotter, drier temperatures in many places — can be very useful for showing how close some plants are to local extinction already. Combined with critical limit data, limited conservation funds could be even more wisely spent, revealing plants’ warning signs before they become visible.

Emory-led study finds emerging ‘forever chemicals’ in homes, drinking water and humans

Photo Credit: Pixabay

A newly released study led by researchers from Emory University’s Rollins School of Public Health was one of the first to find an emerging class of “forever chemicals” in the homes, drinking water and bodies of United States residents.

There are thousands of per- and polyfluoroalkyl substances (PFAS), also known as “forever chemicals,” but scientists and health care experts only have sufficient data on the potential human-health impacts of a relative handful of these man-made chemical compounds. Most of the existing research has focused on the legacy and longer-chain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), which were found to be toxic and have been banned for many years. 

However, an Emory-led study published in Environmental Science & Technology found that an emerging class of ultrashort-” and short-chain PFAS – meant to serve as replacements for the already banned PFAS compounds – are now being found in elevated levels in U.S. residents, as well as their homes and water supplies.  Ultrashort- and short-chain PFAS have fewer carbons and are more mobile, particularly in water, than legacy PFAS.

Scientists and philosophers team up to study concept of evolution beyond biological context

As Earth formed, new geologic processes, especially those related to the interaction of hot fluids with rock during igneous activity and plate tectonics, gave birth to over 1500 new mineral species (4.55 to 2.5 billion years ago). At 2.5 billion years ago, emerging biological life introduced oxygen into the atmosphere. This was a time of pivotal change, when photosynthesis began and the interaction of iron with oxygen-based minerals changed ancient life, providing the blueprint for our future evolution, together with minerals. With the progress of the evolution of life from single-celled to multicelled organisms, and the formation of ecosystems, the mineralogy of the surface of the earth became more complex. The mineral diversity that was created fundamentally changed the direction and possibilities of evolution. Biodiversity leads to mineral diversity, and vice versa. The two systems, biological and mineral, interacted to create life as we know it today
Photo Credit: Dr. Robert Lavinsky

A new paper from an interdisciplinary team led by Carnegie’s Michael Wong and Robert Hazen explores the idea of increasing complexity in natural systems through the lens of evolution. Their work, published by Proceedings of the National Academy of Sciences hypothesizes the existence of “a missing law of nature.”

Their work proposes that complex natural systems evolve to states of greater patterning, diversity, and complexity. In other words, they say that evolution is not limited to life on Earth, it also occurs in other massively complex systems, from planets and stars to atoms, minerals, and more.

Authored by a nine-member team—scientists from Carnegie, Caltech, and Cornell University, and philosophers from the University of Colorado—the work was funded by the John Templeton Foundation.

“Macroscopic” laws of nature describe and explain phenomena experienced daily in the natural world. Natural laws related to forces and motion, gravity, electromagnetism, and energy, for example, were described more than 150 years ago.

New Polymer Membranes, AI Predictions Could Dramatically Reduce Energy, Water Use in Oil Refining

A sample of a DUCKY polymer membrane researchers created to perform the initial separation of crude oils using significantly less energy.
Photo Credit: Candler Hobbs

A new kind of polymer membrane created by researchers at Georgia Tech could reshape how refineries process crude oil, dramatically reducing the energy and water required while extracting even more useful materials.

The so-called DUCKY polymers — more on the unusual name in a minute — are reported in Nature Materials. And they’re just the beginning for the team of Georgia Tech chemists, chemical engineers, and materials scientists. They also have created artificial intelligence tools to predict the performance of these kinds of polymer membranes, which could accelerate development of new ones.

The implications are stark: the initial separation of crude oil components is responsible for roughly 1% of energy used across the globe. What’s more, the membrane separation technology the researchers are developing could have several uses, from biofuels and biodegradable plastics to pulp and paper products.

“We’re establishing concepts here that we can then use with different molecules or polymers, but we apply them to crude oil because that’s the most challenging target right now,” said M.G. Finn, professor and James A. Carlos Family Chair in the School of Chemistry and Biochemistry.

High-performance Magnesium-Air Primary Battery with Nitrogen-doped Nanoporous Graphene as Air Electrodes

Magnesium (Mg) is one of the most readily available battery materials. Using brine as the electrolyte with carbon-based cathodes, Mg-air primary batteries can be constructed at a low cost. Researchers at the University of Tsukuba employed nanoporous graphene electrodes and a solid electrolyte to obtain a battery with performance equivalent or even superior to those of platinum electrode-based batteries.
Image Credit:  © Yoshikazu Ito

In pursuit of a carbon-neutral society, advancement of battery technology becomes imperative. Primary batteries, though nonrechargeable, hold promise as power sources for sensors and disaster scenarios because of their cost-effective production and voltage stability. However, most of these batteries employ expensive metal electrodes, such as lithium electrodes, necessitating exploration of alternative electrode materials.

Using carbon-based materials for the cathode, magnesium (Mg) for the anode, oxygen from the atmosphere as the cathode active material, and brine for the electrolyte, Mg-air primary batteries can be constructed using inexpensive and abundant materials. Theoretically, these batteries are expected to match lithium-air batteries with regard to performance. However, they do not perform well in terms of battery capacity and operational stability.

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