An international team of scientists from NUST MISIS (Russia), Linköping University (Sweden) and University of Bayreuth (Germany) found that, contrary to the usual physical and chemical laws, the structure of some materials does not condense at ultrahigh pressures. Actually, it forms a porous framework filled with gas molecules. This happened with samples of Os, Hf, and W put together with N in a diamond anvil at a pressure of one million atmospheres. The discovery is described in Angewandte Chemie.
“You can transform a pencil lead into diamond if you squeeze it very hard” — this fact heard by many of us in childhood sounded like a complete nonsense. However, science laws make it clear that there is no miracle: both pencil lead and diamond are formed by the same chemical element, i.e. carbon, which actually forms a different crystal structure under very high pressure. It makes sense: ar pressure the empty space between atoms decreases and the material becomes denser. Until recently, this statement could be applied to any material.
It turned out that a number of materials can become porous at ultrahigh pressure. Such a conclusion was made by a group of scientists from NUST MISIS (Russia), Linköping University (Sweden) and University of Bayreuth (Germany). The team examined three metals (hafnium Hf, tungsten W, and osmium Os) with an addition of N when placed in a diamond anvil at a pressure of 1 million atmospheres, which corresponds to a pressure at a depth of 2.5 thousand kilometers underground. Scientists believe that it was the combination of pressure and nitrogen N that influenced the formation of a porous framework in the crystal lattice.
“Nitrogen itself is quite inert and without ultrahigh pressure it would not react with these metals in any way. Materials without nitrogen would simply condense in a diamond anvil. However, a combination gave an amazing result: some of the nitrogen atoms formed a kind of reinforcing framework in the materials, allowing the formation of pores in the crystal lattice. Consequently, additional nitrogen molecules entered the space”, said Professor Igor Abrikosov, head of the theoretical research group and NUST MISIS Laboratory for the Modeling and Development of New Materials.
The experiment was initially conducted physically by Sweden and German part of the group, and then its results were confirmed by theoretical modeling on NUST MISIS supercomputer. Scientists emphasize that the research is fundamental, i.e. materials with such properties are not yet created for specific tasks. At the moment, the very fact that previously unthinkable modifications of materials can be obtained is important.
A whole new step will be to preserve such materials at normal atmospheric pressure. In one of the previous works, scientists managed to preserve a special modification of rhenium nitride. Currently, rapid cooling to critical low temperatures is considered as one of the ways to stabilize new materials.
References: Maxim Bykov et al, High‐Pressure Synthesis of Metal–Inorganic Frameworks Hf 4 N 20 ⋅N 2 , WN 8 ⋅N 2 , and Os 5 N 28 ⋅3 N 2 with Polymeric Nitrogen Linkers, Angewandte Chemie International Edition (2020). DOI: 10.1002/anie.202002487
Further development of this technique will lead to novel methods to predict stages of manifestation of diseases like cancer, atherosclerosis, and fibrosis from simple tissue fluids or blood samples.
Every biological system is naturally equipped with a defense mechanism to protect against abnormal changes caused by either local, environmental, or biochemical alteration. White blood cells (WBC) play the role of such a ‘soldier’ in our immune response. One type of WBC, known as macrophages, is the most efficient and specialized fighter since it is simultaneously equipped with the power of selective identification and elimination of foreign invaders, as well as the potency to repair wounds. Depending on their work distribution, macrophages are mainly comprised of two types, M1 and M2. M1 cells act as the ‘professional killer’, while M2 cells are more concentrated on healing activity.
In a normal, healthy situation, the immune system maintains a good balance between M1 and M2 cells. But in diseased conditions like bacterial, virus or parasite infections, or inflammations for atherosclerosis, cancer, or arthritis, the balance between M1 and M2 becomes affected, and depending on the crisis, a particular shift in M1 or M2 population occurs. If such changes could be monitored, it would lead to easy diagnostics and prediction of health conditions. There is currently no tool that can provide easy detection of M1/M2 cells directly from tissue fluid or a blood sample in a label-free manner without fluorescent tagging.
In a study just published in the journal Nano Letters, researchers from Bar-Ilan University in Israel have shown a simple solution to this issue with the help of the scattering effect of Gold Nanorods (GNRs). Gold-based nanoparticles are well known for their prominent optical property with high absorbance and scattering effects. By manipulating the scattering effect and adjusting the surface coating of GNRs, the researchers were able to identify changes in the optical property of M1 and M2 macrophages and utilize them as a parameter to monitor physiological changes.
The researchers used the flow cytometer (FCM) to capture changes in the granularity of the cells in order to identify GNR-laden macrophages and determine the specific scattering of GNRs. The FCM is generally used to identify a particular population of fluorescence-labeled cells, but in this case, it was used in label-free detection based only on scattering that came from the GNRs. With this unique method the researchers observed that one type of coating of GNRs exhibited greater selectivity towards M2 cells over M1.
“Our approach in utilizing the scattering of GNRs to identify M1 and M2 macrophages opens a new strategy in cellular identifications using FCM with the help of increased scattering of internalized nanoparticles,” says Dr. Ruchira Chakraborty, leading researcher at Prof. Dror Fixler’s laboratory at Bar-Ilan University’s the Kofkin Faculty of Engineering and Institute of Nanotechnology and Advanced Materials. “Further development of this technique will lead us to build a new point of care or a biopsy tool which can predict the stages of manifestation of diseases like cancer, atherosclerosis, and fibrosis just from the simple tissue fluids or blood samples,” says Prof. Dror Fixler, Director of the Bar-Ilan Nano Institute, who led the study in cooperation with Prof. Ran Kornowski and Dr. Dorit Leshem from Beilinson Hospital.
References: Ruchira Chakraborty et al, The Scattering of Gold Nanorods Combined with Differential Uptake, Paving a New Detection Method for Macrophage Subtypes Using Flow Cytometery, Nano Letters (2020). DOI: 10.1021/acs.nanolett.0c03525
Study shows using intranasal delivery method may reduce inflammation in the brain.
Intranasal administration of an anti-inflammatory drug helped reduce disease progression in a preclinical model of multiple sclerosis, according to recent research out of the University of Alberta.
Christopher Power, professor in the Faculty of Medicine & Dentistry, and Leina Saito, a graduate student on his team, showed that delivering an anti-inflammatory drug to mice helped prevent damage to brain cells, effectively slowing the progression of the disease.
MS is a devastating illness with no known cause and no cure. Power’s lab seeks to better understand the disease to develop effective treatments.
“Nerves in the brain are like insulated wires, but in MS there is initially a loss of the insulation [called myelin], and then the eventual loss of the wire. Those losses are caused by inflammation. That inflammation, which we think is the driving force for MS, is our main research interest,” said Power, a neurologist in the Northern Alberta MS Clinic, co-director of the U of A’s MS Centre and member of the Neuroscience and Mental Health Institute.
His research group is particularly interested in inflammasomes, molecules that are responsible for the activation of an inflammatory response in the body. For a disease such as MS, that response must be controlled to halt the progression. Power’s lab identified a drug called VX-765 as a strong candidate therapy for MS patients.
The drug works by inhibiting caspase-1, a component of inflammasomes that promotes harmful inflammation in the body. In previous research, Power’s group saw beneficial results by delivering insulin intranasally in other models of brain inflammation, and he decided to go with that delivery route again. Using mouse models, Power dissolved VX-765 in a fluid and then injected the mixture into the nose.
“It’s a lot easier for patients because you need less of the drug. It’s a direct delivery into the brain, it doesn’t go into the circulatory system and it’s not broken down as quickly,” said Power of the intranasal delivery method.
To examine the impact of VX-765 on the nerves, Power collaborated with researcher Frank Wuest, interim chair in the U of A’s Department of Oncology and member of the Cancer Research Institute of Northern Alberta. Wuest is a world expert on positron emission tomography (PET) scanning, an imaging technique that uses radioactive substances to visualize changes in the body. Wuest used PET scans to look at brain metabolism and was able to document whether the insulation had been stripped or not after the therapeutic was delivered.
“The study shows intranasal therapy is effective in preventing demyelination and axon injury and loss, so that’s a real tonic for us to keep going,” said Power. “The loss of myelin and loss of nerves are irreversible processes, so any therapeutic that helps to slow or prevent that from happening is an exciting advance for MS research. The particular delivery method also allows the therapy to be delivered in a more precise and targeted way.”
A newly proposed component — the biodynamic interface — may better explain how humans interact with their environment.
Researchers at Mount Sinai have proposed a groundbreaking new way to study the interaction between complex biological systems in the body and the environment. Their theory suggests the existence of “biodynamic interfaces,” an intermediate entity between the two realms, as opposed to conventional approaches that analyze individual aspects of the interaction between the environment and humans in isolation, according to a paper published in BioEssays in October.
The environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. The Mount Sinai scientists believe that such complex systems cannot interact directly, but rather that their interaction requires the formation of an intermediary “interface.” The scientists believe that this theory will lead to the establishment of a new field, “environmental biodynamics,” that will advance the way the environment and human health are studied.
The basis of their theory arose when they compared the time period when autistic children were exposed to toxins to how the children’s brains functioned afterward. At the same time, they found distinct patterns in the intake and metabolism of essential elements and toxins, which were dependent not only on the timing and magnitude of the environmental exposure but also on what was happening within the biological systems of the child’s body.
“These rhythms were driven by the properties of both the biological and environmental systems, but exhibited properties independent of either system,” said Manish Arora, PhD, the Edith J. Baerwald Professor and Vice Chair of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “They supported the existence of an interface mediating the interaction of biological and environmental systems. The interface itself, which applies constraints and passes information between interacting systems, must be the subject of inquiry because without refocusing the attention on biodynamic interfaces, how the environment impacts health cannot be discerned.”
The study of the interface will allow scientists to better understand how complex systems like the environment and human physiology affect each other. Current methods using plain analysis are incomplete, the scientists say.
“The standard course of inquiry measures some aspect of the environment like lead in the water, and we’d link this to some aspect in human development like IQ,” said Paul Curtin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, an author on the paper. “We’ve learned a lot from environmental health using this approach, but it has its limits.”
This interface also considers social, behavioral, and cultural dynamics to be a particularly fruitful avenue of research. This new theory would allow scientists to assess the interface between income and other processes, including health outcomes using dynamical systems methods. It would also define how human activities could negatively influence the environment and negatively influence their own health outcomes and further environmental impacts over time.
Dr. Arora’s work was funded by a prestigious Revolutionizing Innovative, Visionary Environmental Health (RIVER) Award from the National Institute of Environmental Health Sciences, totaling $8 million over eight years to complete research on the biodynamic interface. Alessandro Giuliani, PhD, Professor of Environmental Health at the University of Rome, has made a significant contribute to the development of the theory.
“Arora, Giuliani, and Curtin’s conjecture is potentially a major breakthrough, as knowing the factors that influence biological time may be the key to understanding why people age or mature at different rates, and how our early life experiences can influence our health as adults,” said Robert O. Wright, MD, MPH, Ethel H. Wise Professor and Chair of Environmental Medicine and Public Health and Director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai.
A new study describes a bioluminescent gene that could be the reason that so-called “sea pickles,” or pyrosomes, an underwater free-floating colony of thousands of tiny animals, reverberate in blue-green light. If confirmed, the finding would be the first bioluminescent gene identified from a chordate–the group that includes all vertebrates as well as a couple types of invertebrates: sea squirts (including pyrosomes) and lancelets. The research is published today in the journal Scientific Reports.
“We know that throughout the tree of life, there are many hundreds of organisms that can produce light and that they do it for a variety of reasons,” said co-author Michael Tessler, an assistant professor at St. Francis College who conducted the research while he was a postdoctoral researcher at the American Museum of Natural History. “Our work suggests that there is a common gene shared among at least some animals that, with a few small changes, could be responsible for this bioluminescence. A baseline gene like this could help explain how many of these very different organisms, like a brittle star and the sea pickle, ended up with the same ability to glow.”
The idea for this study arose in 2017 when co-author David Gruber, a Museum research associate and a Presidential Professor at Baruch College, was off the coast of Brazil testing a new collecting tool outfitted to a submersible: squishy robotic hands meant to gently grab delicate sea creatures. The expedition team, which included Museum Curator John Sparks and was funded by the Dalio Family Foundation and OceanX, collected a selection of sausage-sized pyrosomes (Pyrosoma atlanticum).
These gelatinous colonies are made of hundreds of tiny animals called zooids–each with a heart and a brain–that work together to move, eat, and breathe. The name pyrosome, which in Greek translates as “fire-body,” is derived from their unique bioluminescent displays, which, unlike many bioluminescent animals, can be triggered by light. While pyrosomes attracted the attention of naturalists in the 17th and 18th centuries, many of the most basic facts about their bioluminescence remain elusive.
“Understanding the biochemical pathway for pyrosome bioluminescence is of particular interest because as a chordate, these animals are much more closely related to vertebrates–and to us as humans–than many of the more traditional bioluminescent creatures that might come to mind, things like jellyfish or fireflies,” Gruber said.
Like other bioluminescent organisms, pyrosomes rely on a chemical reaction between a substrate (luciferin) and a gene (luciferase) to produce light. The researchers found that mixing a common type of luciferin, called coelenterazine, with Pyrosoma atlanticum resulted in bioluminescence. To further investigate the inner workings of this reaction, they sequenced the RNA of the pyrosomes collected in Brazil as well as from additional specimens found in a large bloom off of Vancouver Island in Canada.
The researchers discovered a gene that matches a luciferase often used in biotechnology that is found in sea pansies, a relative of jellyfish, anemones, and corals. They confirmed that the newly discovered pyrosome gene does, indeed, produce light by expressing it in a bacterial colony and adding coelenterazine.
“Being a part of this study felt like being a part of a century-old mystery novel as to how the pyrosome glows in the dark,” said Jean Gaffney, a co-author and assistant professor at Baruch College. “I have never worked with a species that was seemingly so alien, but as a chordate is strikingly similar to us.”
A similar gene was recently predicted from a bioluminescent brittle star, indicating that these types of luciferases may have evolved convergently from a baseline gene.
“This study advances the debate about pyrosome bioluminescence,” Tessler said. “We provide justification for the idea that this animal produces its own light and it might be able to do so because of a pattern of evolution that as repeated throughout the animal tree of life.”
References: Michael Tessler et al, A putative chordate luciferase from a cosmopolitan tunicate indicates convergent bioluminescence evolution across phyla, Scientific Reports (2020). DOI: 10.1038/s41598-020-73446-w
A microRNA that can be found in a blood sample may make it easier to detect gastric cancer and could lead to improved treatment for diseases that are resistant to common immunotherapies.
A promising new biomarker that appears in patients before stomach cancer develops may help with early detection of the disease and improve patient response to therapy, according to findings in a study led by University of Arizona Health Sciences researchers.
The biomarker can be detected through a simple blood test, saving time and lowering costs. Currently, stomach cancer diagnosis requires endoscopic collection of stomach tissue through a biopsy procedure, and then analysis by pathology.
Published in Gut, the journal of the British Society of Gastroenterology, the study was led by Juanita L. Merchant, MD, PhD, chief of the Division of Gastroenterology and Hepatology at the UArizona College of Medicine – Tucson, a cancer biology program researcher at the UArizona Cancer Center and an elected member of the National Academy of Medicine.
The biomarker, MiR130b, is a microRNA – or small non-coding RNA molecule that can play an important role in regulating gene expression, affecting disease development and progression. MiR130b can be produced by a group of immune cells called myeloid-derived suppressor cells (MDSCs), commonly associated with infections caused by Helicobacter pylori (H. pylori), a bacteria associated with ulcers. These particular cell types in the stomach correlate with early, preneoplastic changes (before a tumor develops) that can lead to gastric cancer long after an H. pylori infection has passed.
The study included collaboration with Yana Zavros, PhD, associate head for research in the College of Medicine – Tucson’s Department of Cellular and Molecular Medicine and the Cancer Center’s shared resource director for Tissue Acquisition Cellular and Molecular Analysis.
“Even though you get can get rid of the bacteria, oftentimes the infection itself already has initiated a cascade of events that inevitably may lead to cancer,” Dr. Zavros said. “That is why early detection is so important.”
A Blood Test Instead of a Procedure
The study arose out of basic science mouse models that simulated changes in the stomach similar to that caused by H. pylori. This led the researchers to identify MiR130b in the mouse models, and they also detected the same microRNA in the plasma of human patients that either had precancerous changes or those that already had progressed to cancer.
“This was a retrospective study,” said Dr. Merchant, who is a member of the university’s BIO5 Institute. “It is very exciting because now we can begin looking at this biomarker more prospectively in different patient populations.”
Although less common in the United States, the National Cancer Institute reports gastric (stomach) cancer is the third most common cause of cancer-related deaths in the world. The findings, however, could have major implications for Arizona’s rural areas and Hispanic and Native American populations, which are at greater risk for developing gastric and other gastrointestinal (GI) cancers, because these diseases often are caused by dietary and environmental factors and may go undetected for long periods.
Dr. Merchant’s lab has a “sub-project” in the Cancer Center’s U54 grant (Partnership for Native American Cancer Prevention) to study detection of the microRNA described in the Gut paper in members of Native American populations with H. pylori.
“This molecular signature (the microRNA – MiR130b) that we discovered may help us see if patients have changes in their mucosa (the membrane that lines the stomach) related to having H. pylori,” Dr. Merchant said. “And a blood sample would be less invasive and then could be a way to make the decision whether we need to bring a patient in for an endoscopy.”
Broader Implications for Treatment
Once diagnosed, gastric cancer can be difficult to treat. Immunotherapies with proven effectiveness in treating other types of cancer are not as successful against most GI cancers, including stomach cancer. The researchers believe these new findings in gastric cancer may help to address why other GI cancers also are resistant to therapy.
“The underlying mechanism by which a patient may not respond well in gastric cancer may be applicable in other organs as well” Dr. Zavros said. “The way the cells interact with each other to render that patient resistant to therapy may be quite similar between gastric, pancreatic and colon cancers.”
Dr. Merchant added: “There may be dual-purposes. We can look at it as a biomarker to help us from a diagnostic perspective, but we also can look at therapies that can be developed based on what this microRNA itself is targeting.”
Another project funded by the Cancer Center’s “Sparking Bench-to-Bedside Team Science Project” award is building from results of this study to explore therapies for pancreatic and gastric cancer. The investigators are exploring the tumor microenvironment, in particular the immune cell MDSCs, referred to previously, that appears to dampen the chemotherapeutic response to immunotherapies.
The project relies heavily on Dr. Zavros’ “BioDroid” program, which develops miniature organs in the lab with a realistic microanatomy, also known as organoids. These are used in collaboration with the Tissue Acquisition Repository for Gastrointestinal and HEpaTic Systems (TARGHETS), created by Dr. Merchant. TARGHETS is a GI/Hepatology biorepository that collects samples from patients who undergo endoscopy.
Both Drs. Zavros and Merchant are looking to the BioDroid and TARGHETS efforts to reveal additional information that will allow them to develop new approaches to address resistance of gastric cancer to immunotherapies.
“We want to find a way to reprogram the cancer cells or the immune cells within that patient’s tumor environment to make the patient more responsive to the therapy,” Dr. Zavros said. “A biomarker gives us a place to start.”
References: Ding L, Li Q, Chakrabarti J, et al MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer Gut 2020;69:1750-1761.Link: https://gut.bmj.com/content/69/10/1750
Inflammatory bowel disease (IBD) affects more than 70,000 children in the United States and the prevalence is rising. In fact, 25% of the 3.1 million individuals with IBD present before 21 years of age. There is no cure for IBD, and treatment often includes medication to block a molecule that causes inflammation in the intestines called tumor necrosis factor (TNF). Unfortunately, the TNF-blocking therapy doesn’t work for many children and its therapeutic effects can be short-lived.
In a new study in Cell Reports, investigators at The Saban Research Institute at Children’s Hospital Los Angeles have uncovered a role that TNF and its receptor play in intestinal health that will lead to a better understanding of TNF. This could positively impact future treatments for patients with IBD.
Children with IBD, a broad term which includes Crohn’s disease and ulcerative colitis, can experience abdominal pain and weight loss, which can impact a child’s growth. Patients with these conditions often have elevated levels of TNF in their bloodstream and intestines.
“Increased expression of TNF is one of the body’s first responses to infection or injury,” says D. Brent Polk, MD, a physician and investigator who studies intestinal development and associated disorders. “In many patients, antibodies that block TNF are effective, but most patients don’t benefit from the therapy long term.”
Sometimes, says Dr. Polk, patients initially show improvement, but then the treatment stops working. Oddly, some children even develop IBD when they receive anti-TNF therapy for an unrelated condition, such as juvenile arthritis.
Dr. Polk’s investigations take a different approach to studying IBD. Instead of viewing TNF signaling as either pro- or anti-IBD, his work examines whether there is a range of TNF levels that maintain intestinal health.
“We know that TNF signaling leads to inflammation,” he says, “but when we blocked the TNF receptor in a pre-clinical model of IBD, it led to early-onset colitis. So, it’s not a simple matter of blocking TNF outright. The body is really fine tuned to maintain health.”
His study shows that the timing of TNF signaling and which receptors are activated developmentally could be more important than merely the levels of the inflammatory molecule.
“It’s not that TNF signaling is ‘good’ or ‘bad,'” explains Dr. Polk. “It’s more complicated than the field previously understood.” He says that TNF does cause inflammation in the intestines, but it also appears to play a protective role, especially early in life.
The study is preclinical but has important implications for patients. Future therapies depend on a better understanding of how molecules like TNF function. Work like Dr. Polk’s could lead to treatments that give relief to all children with IBD.
For the first time, researchers have mapped the biological diversity of marine sediment, one of Earth’s largest global biomes. Although marine sediment covers 70% of the Earth’s surface, little was known about its global patterns of microbial diversity.
A team of researchers from the Japan Agency for Marine-Earth Science and Technology (JAMSTEC), the University of Hyogo, the University of Kochi, the University of Bremen, and the University of Rhode Island delineated the global diversity of microbes in marine sediment. For the study, published in the Proceedings of the National Academy of Sciences, Tatsuhiko Hoshino, senior researcher at JAMSTEC, and his colleagues including URI Graduate School of Oceanography Professor Steven D’Hondt analyzed 299 samples of marine sediment collected as core samples from 40 sites around the globe. Their sample depths ranged from the seafloor to 678 meters below it. To accurately determine the diversity of microbial communities, the authors extracted and sequenced DNA from each frozen sample under the same clean laboratory condition.
The 16S rRNA gene sequences (approximately 50 million sequences) obtained through comprehensive next-generation sequencing were analyzed to determine microbial community composition in each sample. From these 50 million sequences, the research team discovered nearly 40,000 different types of microorganisms in marine sediment, with diversity generally decreasing with depth. The team found that microbial community composition differs significantly between organic-rich sediment of continental margins and nutrient-poor sediment of the open ocean, and that the presence or absence of oxygen and the concentration of organic matter are major factors in determining community composition.
By comparing their results to previous studies of topsoil and seawater, the researchers discovered that each of these three global biomes–marine sediment, topsoil, and seawater–has different microbial communities but similar total diversity. “It was an unexpected discovery that microbial diversity in the dark, energy-limited world beneath the seafloor is as diverse as in Earth’s surface biomes,” said Hoshino.
Furthermore, by combining the estimates of bacterial and archaeal diversity for these three biomes, the researchers found that bacteria are far more diverse than archaea–microbes distinct from bacteria and known for living in extreme environments–on Earth.
“In this respect as well, microbial diversity in the dark realm of marine sediment resembles microbial diversity in the surface world,” said D’Hondt. “It’s exciting to glimpse the biological richness of this dark world.”
References: Tatsuhiko Hoshino, Hideyuki Doi, Go-Ichiro Uramoto, Lars Wörmer, Rishi R. Adhikari, Nan Xiao, Yuki Morono, Steven D’Hondt, Kai-Uwe Hinrichs, Fumio Inagaki, “Global diversity of microbial communities in marine sediment”, Proceedings of the National Academy of Sciences Oct 2020, 201919139; DOI: 10.1073/pnas.1919139117
For the first time, scientists have added microscopic tracking devices into the interior of cells, giving a peek into how development starts.
For the first time, scientists have introduced minuscule tracking devices directly into the interior of mammalian cells, giving an unprecedented peek into the processes that govern the beginning of development.
This work on one-cell embryos is set to shift our understanding of the mechanisms that underpin cellular behaviour in general, and may ultimately provide insights into what goes wrong in ageing and disease.
The research, led by Professor Tony Perry from the Department of Biology and Biochemistry at the University of Bath in the UK, involved injecting a silicon-based nanodevice together with sperm into the egg cell of a mouse. The result was a healthy, fertilised egg containing a tracking device.
The tiny devices are a little like spiders, complete with eight highly flexible ‘legs’. The legs measure the ‘pulling and pushing’ forces exerted in the cell interior to a very high level of precision, thereby revealing the cellular forces at play and showing how intracellular matter rearranged itself over time.
The nanodevices are incredibly thin – similar to some of the cell’s structural components, and measuring 22 nanometres, making them approximately 100,000 times thinner than a pound coin. This means they have the flexibility to register the movement of the cell’s cytoplasm as the one-cell embryo embarks on its voyage towards becoming a two-cell embryo.
“This is the first glimpse of the physics of any cell on this scale from within,” said Professor Perry. “It’s the first time anyone has seen from the inside how cell material moves around and organises itself.”
WHY PROBE A CELL’S MECHANICAL BEHAVIOUR?
The activity within a cell determines how that cell functions, explains Professor Perry. “The behaviour of intracellular matter is probably as influential to cell behaviour as gene expression,” he said. Until now, however, this complex dance of cellular material has remained largely unstudied. As a result, scientists have been able to identify the elements that make up a cell, but not how the cell interior behaves as a whole.
“From studies in biology and embryology, we know about certain molecules and cellular phenomena, and we have woven this information into a reductionist narrative of how things work, but now this narrative is changing,” said Professor Perry. The narrative was written largely by biologists, who brought with them the questions and tools of biology. What was missing was physics. Physics asks about the forces driving a cell’s behaviour, and provides a top-down approach to finding the answer.
“We can now look at the cell as a whole, not just the nuts and bolts that make it.”
Mouse embryos were chosen for the study because of their relatively large size (they measure 100 microns, or 100-millionths of a metre, in diameter, compared to a regular cell which is only 10 microns [10-millionths of a metre] in diameter). This meant that inside each embryo, there was space for a tracking device.
The researchers made their measurements by examining video recordings taken through a microscope as the embryos developed. “Sometimes the devices were pitched and twisted by forces that were even greater than those inside muscle cells,” said Professor Perry. “At other times, the devices moved very little, showing the cell interior had become calm. There was nothing random about these processes – from the moment you have a one-cell embryo, everything is done in a predictable way. The physics is programmed.”
The results add to an emerging picture of biology that suggests material inside a living cell is not static, but instead changes its properties in a pre-ordained way as the cell performs its function or responds to the environment. The work may one day have implications for our understanding of how cells age or stop working as they should, which is what happens in disease.
The study is published this week in Nature Materials and involved a trans-disciplinary partnership between biologists, materials scientists and physicists based in the UK, Spain and the USA.
The study is published this week in Nature Materials and involved a trans-disciplinary partnership between embryologists in Bath and the USA led by Professor Perry, and materials scientists and physicists led by Professor José Antonio Plaza at the Instituto de Microelectrónica de Barcelona (IMB-CNM) in Spain.
References: Duch M, Torras N, Asami M, Suzuki T, Arjona MI, Gómez-Martínez R, VerMilyea MD, Castilla R, Plaza JA, Perry ACF. Tracking intracellular forces and mechanical property changes in mouse one-cell embryo development. Nat Mater. 2020 Oct;19(10):1114-1123. doi: 10.1038/s41563-020-0685-9. Epub 2020 May 25. PMID: 32451513.