Sunday, December 04, 2022

Mom’s dietary fat rewires male and female brains differently

Excess fat triggers immune cells to overeat serotonin in the brain of developing male mice, leading to depression-like behavior

Peer-Reviewed Publication

DUKE UNIVERSITY

Microglia Sequesters Serotonin 

IMAGE: A MICROGLIA (IN MAGENTA) FROM A MALE MOUSE BORN TO A MOM ON A HIGH-FAT DIET, WHICH SEQUESTERS MORE BRAIN SEROTONIN (IN GREEN) THAN MALES WITH MOM’S EATING A TYPICAL LAB DIET. THE BLUE IS THE GLIA’S NUCLEUS. view more 

CREDIT: STACI BILBO LAB, DUKE UNIVERSITY

DURHAM, NC -- More than half of all women in the United States are overweight or obese when they become pregnant. While being or becoming overweight during pregnancy can have potential health risks for moms, there are also hints that it may tip the scales for their kids to develop psychiatric disorders like autism or depression, which often affects one gender more than the other.

What hasn’t been understood however is how the accumulation of fat tissue in mom might signal through the placenta in a sex-specific way and rearrange the developing offspring’s brain.

To fill this gap, Duke postdoctoral researcher Alexis Ceasrine, Ph.D., and her team in the lab of Duke psychology & neuroscience professor Staci Bilbo, Ph.D., studied pregnant mice on a high-fat diet. In findings appearing November 28 in the journal Nature Metabolism, they found that mom’s high-fat diet triggers immune cells in the developing brains of male but not female mouse pups to overconsume the mood-influencing brain chemical serotonin, leading to depressed-like behavior.

The researchers said a similar thing may be happening in humans, too.

People with mood disorders like depression often lose interest in pleasurable activities. For mice, one innately pleasurable activity is drinking sugar water. Since mice preferentially sip sugar water over plain tap when given the choice, Ceasrine measured their drink preference as an estimate for depression. Males, but not females, born by moms on a high-fat diet lacked a preference for simple syrup over tap water. This rodent-like depression suggested to Ceasrine that mom’s nutrition while pregnant must have changed their male offspring’s brain during development.

One immediate suspect was serotonin. Often called the “happy” chemical, serotonin is a molecular brain messenger that’s typically reduced in people with depression.

Ceasrine and her team found that depressed-like male mice from high-fat diet moms had less serotonin in their brain both in the womb and as adults, suggesting these early impacts have lifelong consequences. Supplementing mom’s high-fat rodent chow with tryptophan, the chemical precursor to serotonin, restored males’ preference for sugar water and brain serotonin levels. Still, it was unclear how fat accumulation in mom lowered serotonin in their offspring.

To get at this, the team investigated the resident immune cells of the brain: microglia.

Microglia are the understudied Swiss Army knives of the brain. Their jobs include serving as a security monitor for pathogens as well as a hearse to haul away dead nerve cells. Microglia also have ample space and appetites to consume healthy brain cells whole.

To see if microglia were overindulging in serotonin, Ceasrine analyzed the contents of their cellular “stomach”, the phagosome, with 3D imaging, and found that males born by moms on high-fat diets had microglia packed with more serotonin than those born to moms on a typical diet. This indicated that elevated fat accumulation during pregnancy somehow signals through the male but not female placenta to microglia and instructs them to overeat serotonin cells. How fat can signal through the placental barrier remained a mystery, though.

One thought was that bacteria were to blame.

“There's a lot of evidence that when you eat a high fat diet, you actually end up with endotoxemia,” Ceasrine said. “It basically means that you have an increase in circulating bacteria in your blood, or endotoxins, which are just parts of bacteria.”

To test if endotoxins could be the critical messenger from mom to enwombed males, the team measured their presence and found that, indeed, high-fat diets during pregnancy beefed up endotoxin levels in the placenta and their offspring’s developing brain. Ceasrine said this may explain how fat accumulation triggers an immune response from microglia by increasing the presence of bacteria, resulting in overconsumed brain cells in male mice.

To see whether this may be true of humans as well, Ceasrine teamed up with Susan Murphy, Ph.D., a Duke School of Medicine associate professor in obstetrics and gynecology, who provided placental and fetal brain tissue from a previous study. Just as the researchers observed in mice, they found that the more fat measured in human placental tissue, the less serotonin was detected in the brains of males but not females.

Bilbo and Ceasrine are now starting to work out how and why female offspring are impacted differently when mom amasses high levels of fat during pregnancy. Fat doesn’t lead to depression in female mice, but it does make them less social, perhaps due to an overconsumption of the pro-social hormone oxytocin, instead of serotonin.

For now, this research highlights that not all placentas are created equally. This work may one day help guide clinicians and parents in better understanding and possible treatment or prevention of the origins of some mood disorders by considering early environmental factors, like fat accumulation during gestation.

So, why would the placenta treat male and female fetuses differently? Ceasrine was initially stumped when a student asked a similar question after a talk she gave to Bilbo’s class. Bilbo laughed and reiterated the question. But now they think they have it figured out.

 “I was hugely pregnant at the time, and I was like, ‘Oh, wait. Pregnancy!’” Ceasrine recalled. “Men never have to carry a fetus, so they never have to worry about the kind of immune response of self versus non-self that you have to do when you're a woman and you carry a baby.”

Support for the research came from the US National Institutes of Health (F32HD104430, R01ES025549), the Robert and Donna Landreth Family Foundation, and the Charles Lafitte Foundation.

CITATION: “Maternal Diet Disrupts the Placenta-Brain Axis in a Sex-Specific Manner,” Alexis M. Ceasrine, Benjamin A. Devlin, Jessica L. Bolton, Lauren A. Green, Young Chan Jo, Carolyn Huynh, Bailey Patrick, Kamryn Washington, Cristina L. Sanchez, Faith Joo, A. Brayan Campos-Salazar, Elana R. Lockshin, Cynthia Kuhn, Susan K. Murphy, Leigh Ann Simmons, Staci D. Bilbo. Nature Metabolism, Nov. 28, 2022. DOI: 10.1038/s42255-022-00693-8

Organ donations, transplants increase on days of largest motorcycle rallies

Findings should serve as alarm to increase safety, prepare for higher demand for trauma care and transplant services

Peer-Reviewed Publication

HARVARD MEDICAL SCHOOL

The number of organ donations and organ transplants goes up markedly during large motorcycle rallies, according to a newly published analysis led by researchers at Harvard Medical School and Massachusetts General Hospital.

The research, which appears Nov. 28 in JAMA Internal Medicine, shows that in the regions where the seven largest motorcycle rallies were held throughout the United States between 2005 and 2021, there were 21 percent more organ donors per day, on average, and 26 percent more transplant recipients per day, on average, during these events, compared with days just before and after the rallies.

Large-scale motorcycle rallies attract hundreds of thousands of attendees, and previous studies have shown that these events are accompanied by increases in traumatic injuries and deaths from motor-vehicle crashes.

For the new study, the researchers wanted to know whether these events corresponded to increases in organ donation and transplantation in the regions where they were held.

The researchers posed several questions, including whether organ donations rose along with trauma-related fatalities. They did. Also, was there a difference in the quality of organs donated due to clinical or demographic differences in donors during rallies. There wasn’t.

“The spikes in organ donations and transplantations that we found in our analysis are disturbing, even if not entirely surprising, because they signal a systemic failure to avoid preventable deaths, which is a tragedy,” said study first author David Cron, HMS clinical fellow in surgery at Mass General. “There is a clear need for better safety protocols around such events.”

“At the same time, it is important for transplant communities in places where these events are held to be aware of the potential for increased organ donors during those periods. Organ donation is often called the gift of life, and we should make sure that we do not squander it and can turn any of these tragic deaths into a chance to potentially save other lives,” added Cron, who is also a research fellow at the Center for Surgery and Public Health at Brigham and Women’s Hospital, where he is part of a group interested in understanding how policy decisions and other factors, both inside and outside of the health care system, affect efforts to improve the supply of organs for transplantation.

Using data from the Scientific Registry of Transplant Recipients for deceased organ donors age 16 years and older involved in a motor vehicle crash and recipients of organs from those donors from March 2005 to September 2021, the researchers estimated changes in the incidence of donation and transplants in regions that hosted rallies.

Researchers analyzed records from 10,798 organ donors and 35,329 recipients in the regions where the featured motorcycle rallies take place. During the days on which rallies were held, there were 406 organ donors and 1,400 transplant recipients in regions near the events. During the four weeks before and after the rallies, there were 2,332 organ donors and 7,714 transplant recipients in those locations.

They compared the dates of rallies with the days before and after the rallies. To rule out the influence of other factors not related to bike rallies, the researchers also compared figures from the rally locations with other regions not affected by the rallies and then looked at trends in the rally regions at other times of the year.

They also compared the demographic and clinical characteristics of the donors and the quality of organs donated during rally and non-rally times. They found no significant differences.

Key characteristics of transplant recipients, such as how long they had been waiting for an organ and how severe their illness was at the time of transplant, were also similar whether there was a rally happening or not. This finding, the researchers noted, indicates that the increase in the number of organs available was not enough to relieve the critical shortage of donor organs that the nation faces, even for a brief period.

Cron also noted that the available data were not detailed enough to say whether the donors perished in motorcycle crashes or in passenger vehicles.

Bike rallies are generally large, crowded events that take place in rural areas or small towns with traffic infrastructure intended for much smaller populations and far less traffic, the researchers noted. This means that to increase overall safety for all motorists and pedestrians, event organizers should pay close attention to overall traffic management in addition to encouraging wearing of helmets and safe motorcycle operation.

The seven motorcycle rallies in the study each draw more than 200,000 visitors over the course of several days. Daytona Bike Week in Florida and the Sturgis Motorcycle Rally in South Dakota are 10-day events that each draw 500,000 visitors.

For the towns that hold the rallies and the people who attend, there are many economic and personal benefits. However, understanding all the possible consequences of an event can help organizers and participants plan better to minimize the risk for unwanted “side effects,” the researchers said.

The paper is the latest in a series by senior author Anupam Jena, the Joseph P. Newhouse Professor of Health Care Policy in the Blavatnik Institute at HMS, examining the often-unanticipated impacts on the health system of large-scale public events. Some of his previous work in this area includes studies that have found that firearm injuries drop nationwide during NRA conventions, that high-risk patients with certain acute heart conditions are more likely to survive than other, similar patients if they are admitted to the hospital during national cardiology meetings, and that people who suffer heart attacks or cardiac arrests in the vicinity of an ongoing major marathon are more likely to die within a month due to delays in transportation to nearby hospitals.

“Nothing in life is ever completely safe. Our priority should be to make risky events like motorcycle rallies as safe as they can be,” Jena said. “But it’s also critical to have a clear understanding of how these events impact the health of individuals and the health care systems that we all rely on so that we can give participants, event organizers, and policymakers the context and data they need to make smart choices.”

Additional authors included Charles Bray and Christopher Worsham of HMS and Joel Adler of Dell Medical School, University of Texas at Austin.

This study was supported by funding from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

 

In utero exposure to maternal injury, associated risk of cerebral palsy

JAMA Pediatrics

Peer-Reviewed Publication

JAMA NETWORK

About The Study: In this study of approximately 2 million births, maternal unintentional injury during pregnancy was associated with an increased risk of cerebral palsy in children, particularly among those who were exposed to maternal injuries that resulted in hospitalization and those who were delivered shortly after the injury. Public health professionals and stakeholders should be aware of these potential long-term consequences on offspring when designing programs and providing recommendations about safety during pregnancy. Early monitoring and developmental assessment of children exposed to maternal injury might be warranted.

Authors: Asma Ahmed, M.D., Ph.D., M.P.H., of the Hospital for Sick Children Research Institute in Toronto, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2022.4535)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2022.4535?guestAccessKey=6d15a7df-af57-4166-9049-40003551ef09&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=112822

Vitamin D supplementation, development among school-age children in an area with vitamin D deficiency

JAMA Pediatrics

Peer-Reviewed Publication

JAMA NETWORK

About The Study: Researchers found in this secondary analysis of a randomized clinical trial including 8,800 school-age children with a high prevalence of vitamin D deficiency that weekly oral administration of vitamin D for 3 years did not influence growth, body composition, or pubertal development. Vitamin D deficiency is prevalent among children living in temperate climates and has been reported to associate independently with stunting and obesity. 

Authors: Davaasambuu Ganmaa, Ph.D., of the Harvard T.H. Chan School of Public Health in Boston, and Adrian R. Martineau, Ph.D., of the Queen Mary University of London, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2022.4581)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2022.4581?guestAccessKey=f4e75ce7-2b65-47b3-a812-4bd41187d0cc&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=112822

Non-detection of key signal allows astronomers to determine what the first galaxies were – and weren’t – like


Gregory (who is a Scotland Yard detective): “Is there any other point to which you would wish to draw my attention?”

Holmes: “To the curious incident of the dog in the night-time.”

Gregory: “The dog did nothing in the night-time.”

Holmes: “That was the curious incident.”


Peer-Reviewed Publication

UNIVERSITY OF CAMBRIDGE

Researchers have been able to make some key determinations about the first galaxies to exist, in one of the first astrophysical studies of the period in the early Universe when the first stars and galaxies formed, known as the cosmic dawn.

Using data from India’s SARAS3 radio telescope, researchers led by the University of Cambridge were able to look at the very early Universe – just 200 million years after the Big Bang – and place limits on the mass and energy output of the first stars and galaxies.

Counterintuitively, the researchers were able to place these limits on the earliest galaxies by not finding the signal they had been looking for, known as the 21-centimetre hydrogen line.

This non-detection allowed the researchers to make other determinations about the cosmic dawn, placing restraints on the first galaxies, enabling them to rule out scenarios including galaxies which were inefficient heaters of cosmic gas and efficient producers of radio emissions.

While we cannot yet directly observe these early galaxies, the results, reported in the journal Nature Astronomy, represent an important step in understanding how our Universe transitioned from mostly empty to one full of stars.

Understanding the early Universe, when the first stars and galaxies formed, is one of the major goals of new observatories. The results obtained using the SARAS3 data are a proof-of-concept study that paves the way to understanding this period in the development of the Universe.

The SKA project – involving two next-generation telescopes due to be completed by the end of the decade – will likely be able to make images of the early Universe, but for current telescopes the challenge is to detect the cosmological signal of the first stars re-radiated by thick hydrogen clouds.

This signal is known as the 21-centimetre line – a radio signal produced by hydrogen atoms in the early Universe. Unlike the recently launched JWST, which will be able to directly image individual galaxies in the early Universe, studies of the 21-centimetre line, made with radio telescopes such as the Cambridge-led REACH (Radio Experiment for the Analysis of Cosmic Hydrogen), can tell us about entire populations of even earlier galaxies. The first results are expected from REACH early in 2023.

To detect the 21-centimetre line, astronomers look for a radio signal produced by hydrogen atoms in the early Universe, affected by light from the first stars and the radiation behind the hydrogen fog. Earlier this year, the same researchers developed a method which they say will allow them to see through the fog of the early universe and detect light from the first stars. Some of these techniques have been already put to practice in the current study.

In 2018, another research group operating the EDGES experiment published a result that hinted at a possible detection of this earliest light. The reported signal was unusually strong compared to what is expected in the simplest astrophysical picture of the early Universe. Recently, the SARAS3 data disputed this detection: the EDGES result is still awaiting confirmation from independent observations.

In a re-analysis of the SARAS3 data, the Cambridge-led team tested a variety of astrophysical scenarios which could potentially explain the EDGES result, but they did not find a corresponding signal. Instead, the team was able to place some limits on properties of the first stars and galaxies.

The results of the SARAS3 analysis are the first time that radio observations of the averaged 21-centimetre line have been able to provide an insight to the properties of the first galaxies in the form of limits of their main physical properties.

Working with collaborators in India, Australia and Israel, the Cambridge team used data from the SARAS3 experiment to look for signals from cosmic dawn, when the first galaxies formed. Using statistical modelling techniques, the researchers were not able to find a signal in the SARAS3 data.

"We were looking for a signal with a certain amplitude,” said Harry Bevins, a PhD student from Cambridge’s Cavendish Laboratory and the paper’s lead author. “But by not finding that signal, we can put a limit on its depth. That, in turn, begins to inform us about how bright the first galaxies were.”

“Our analysis showed that the hydrogen signal can inform us about the population of first stars and galaxies,” said co-lead author Dr Anastasia Fialkov from Cambridge’s Institute of Astronomy. “Our analysis places limits on some of the key properties of the first sources of light including the masses of the earliest galaxies and the efficiency with which these galaxies can form stars. We also address the question of how efficiently these sources emit X-ray, radio and ultraviolet radiation.”

“This is an early step for us in what we hope will be a decade of discoveries about how the Universe transitioned from darkness and emptiness to the complex realm of stars, galaxies and other celestial objects we can see from Earth today,” said Dr Eloy de Lera Acedo from Cambridge’s Cavendish Laboratory, who co-led the research.

The observational study, the first of its kind in many respects, excludes scenarios in which the earliest galaxies were both more than a thousand times as bright as present galaxies in their radio-band emission and were poor heaters of hydrogen gas.

“Our data also reveals something which has been hinted at before, which is that the first stars and galaxies could have had a measurable contribution to the background radiation that appeared as a result of the Big Bang and which has been travelling towards us ever since,” said de Lera Acedo, “We are also establishing a limit to that contribution.”

“It’s amazing to be able to look so far back in time – to just 200 million years after the Big Bang- and be able to learn about the early Universe,” said Bevins.

The research was supported in part by the Science and Technology Facilities Council (STFC), part of UK Research & Innovation (UKRI), and the Royal Society. The Cambridge authors are all members of the Kavli Institute for Cosmology in Cambridge.

CTHULHU STUDIES

Unique features of octopus create ‘an entirely new way of designing a nervous system’

Peer-Reviewed Publication

UNIVERSITY OF CHICAGO MEDICAL CENTER

Octopus INCs cross in the body of the animal 

IMAGE: A HORIZONTAL A SLICE AT THE BASE OF THE ARMS (LABELED AS A) SHOWING THE ORAL INCS (LABELED AS O) CONVERGING AND CROSSING. view more 

CREDIT: KUUSPALU ET AL., CURRENT BIOLOGY, 2022

Octopuses are not much like humans — they are invertebrates with eight arms, and more closely related to clams and snails. Still, they have evolved complex nervous systems with as many neurons as in the brains of dogs, and are capable of a wide array of complicated behaviors. In the eyes of Melina Hale, PhD, and other researchers in the field, this means they provide a great opportunity to explore how alternative nervous system structures can serve the same basic functions of limb sensation and movement.

Now, in a new study published on November 28 in Current Biology, Hale, William Rainey Harper Professor of Organismal Biology and Vice Provost at UChicago, and her colleagues have described something new and totally unexpected about the octopus nervous system: a structure by which the intramuscular nerve cords (INCs), which help the animal sense its arm movement, connect arms on the opposite sides of the animal.

The startling discovery provides new insights into how invertebrate species have independently evolved complex nervous systems. It can also provide inspiration for robotic engineering, such as new autonomous underwater devices.

“In my lab, we study mechanosensation and proprioception — how the movement and positioning of limbs is sensed,” said Hale. “These INCs have long been thought to be proprioceptive, so they were an interesting target for helping to answer the kinds of questions our lab is asking. Up until now, there hasn’t been a lot of work done on them, but past experiments had indicated that they’re important for arm control.”

Thanks to the support for cephalopod research offered by the Marine Biological Laboratory, Hale and her team were able to use young octopuses for the study, which were small enough to allow the researchers to image the base of all eight arms at once. This let the team trace the INCs through the tissue to determine their path.

These octopuses were about the size of a nickel or maybe a quarter, so it was a process to affix the specimens in the right orientation and to get the angle right during the sectioning [for imaging],” said Adam Kuuspalu, a Senior Research Analyst at UChicago and the lead author on the study.

Initially the team was studying the larger axial nerve cords in the arms, but began to notice that the INCs didn’t stop at the base of the arm, but rather continued out of the arm and into the body of the animal. Realizing that little work had been done to explore the anatomy of the INCs, they began to trace the nerves, expecting them to form a ring in the body of the octopus, similar to the axial nerve cords.

Through imaging, the team determined that in addition to running the length of each arm, at least two of the four INCs extend into the body of the octopus, where they bypass the two adjacent arms and merge with the INC of the third arm over. This pattern means that all the arms are connected symmetrically.

It was challenging, however, to determine how the pattern would hold in all eight arms. “As we were imaging, we realized, they’re not all coming together as we expected, they all seem to be going in different directions, and we were trying to figure out how if the pattern held for all of the arms, how would that work?” said Hale. “I even got out one of those children’s toys — a Spirograph — to play around with what it would look like, how it would all connect in the end. It took a lot of imaging and playing with drawings while we wracked our brains about what could be going on before it became clear how it all fits together.”

The results were not at all what the researchers expected to find.

“We think this is a new design for a limb-based nervous system,” said Hale. “We haven’t seen anything like this in other animals.”

The researchers don’t yet know what function this anatomical design might serve, but they have some ideas. “Some older papers have shared interesting insights,” said Hale. “One study from the 1950s showed that when you manipulate an arm on one side of the octopus with lesioned brain areas, you’ll see the arms responding on the other side. So it could be that these nerves allow for decentralized control of a reflexive response or behavior. That said, we also see that fibers go out from the nerve cords into the muscles all along their tracts, so they might also allow for a continuity of proprioceptive feedback and motor control along their lengths.”

The team is currently conducting experiments to see if they can gain insights into this question by parsing out the physiology of the INCs and their unique layout. They are also studying the nervous systems of other cephalopods, including squid and cuttlefish, to see if they share similar anatomy.

Ultimately, Hale believes that in addition to illuminating the unexpected ways an invertebrate species might design a nervous system, understanding these systems can aid in the development of new engineered technologies, such as robots.

“Octopuses can be a biological inspiration for the design of autonomous undersea devices,” said Hale. “Think about their arms — they can bend anywhere, not just at joints. They can twist, extend their arms, and operate their suckers, all independently. The function of an octopus arm is a lot more sophisticated than ours, so understanding how octopuses integrate sensory motor information and movement control can support the development of new technologies.”

The study, “Multiple nerve cords connect the arms of octopus providing alternative paths for inter-arm signaling,” was supported by the US Office of Naval Research (N00014-22-1-2208). Samantha Cody of the University of Chicago was also an author on the paper.

 

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About the University of Chicago Medicine & Biological Sciences

The University of Chicago Medicine, with a history dating back to 1927, is one of the nation’s leading academic health systems. It unites the missions of the University of Chicago Medical Center, Pritzker School of Medicine and the Biological Sciences Division. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine. Its main Hyde Park campus is home to the Center for Care and Discovery, Bernard Mitchell Hospital, Comer Children’s Hospital and the Duchossois Center for Advanced Medicine. It also has ambulatory facilities in Orland Park, South Loop, Homewood and River East as well as affiliations and partnerships that create a regional network of care. UChicago Medicine offers a full range of specialty-care services for adults and children through more than 40 institutes and centers including an NCI-designated Comprehensive Cancer Center. Together with Harvey-based Ingalls Memorial, UChicago Medicine has 1,296 licensed beds, nearly 1,300 attending physicians, over 2,800 nurses and about 970 residents and fellows.

Visit UChicago Medicine’s health and science news blog at www.uchicagomedicine.org/forefront.

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Learning from pangolins and peacocks: Researchers explore next-gen structural materials

Peer-Reviewed Publication

UNIVERSITY OF COLORADO AT BOULDER

From pangolin scales that can stand up to hard hits to colorful but sturdy peacock feathers, nature can do a lot with a few simple molecules.

In a new review paper, a team of international researchers have laid out how engineers are taking inspiration from the biological world—and designing new kinds of materials that are potentially tougher, more versatile and more sustainable than what humans can make on their own.

“Even today, nature makes things way simpler and way smarter than what we can do synthetically in the lab,” said Dhriti Nepal, first author and a research materials engineer at the Air Force Research Laboratory in Ohio. 

Nepal along with Vladimir Tsukruk from Georgia Institute of Technology and Hendrik Heinz of the University of Colorado Boulder served as co-corresponding authors for the new analysis. The team published its findings Nov. 28 in the journal Nature Materials.

The researchers, who come from three countries, delve into the promise and challenges behind “bioinspired nanocomposites.” These materials mix together different kinds of proteins and other molecules at incredibly small scales to achieve properties that may not be possible with traditional metals or plastics. Researchers often design them using advanced computer simulations or models. Examples include thin films that resist wear and tear by incorporating proteins from silkworm cocoons; new kinds of laminates made from polymers and clay materials; carbon fibers produced using bioinspired principles; and panes of glass that don’t easily crack because they include nacre—the iridescent lining inside many mollusk shells.  

Such nature-inspired materials could, one day, lead to new and better solar panels, soft robots and even coatings for hypersonic jets, said Heinz, professor of chemical and biological engineering at CU Boulder. But first, researchers will need to learn how to build them from the bottom up, ensuring that every molecule is in the right place.

“One of the main challenges in this field is how do we structure these materials down to the atomic level,” Heinz said. “We need to know how nature does it so we can try it in the lab and use guidance from computational models.”

The amazing keratin

In the new study, Nepal, Tsukruk, Heinz and their colleagues take a close look at keratin, one of nature’s most adaptable building blocks.

These simple proteins, which often form into twisting helical shapes like DNA, can join together in different ways to make a huge variety of structures—from human fingernails and hair to porcupine quills, rhinoceros horns and the overlapping scales of pangolins.

“Keratin is everywhere, and we’ve hardly even begun to appreciate its utility,” Nepal said.

That’s one of nature’s secrets, she added: Biological materials can exhibit a wide array of complex architectures at many levels—what engineers call “hierarchical” engineering. Some of those structures are large enough to see with the naked eye, while others are so small researchers need powerful microscopes to study them.

The keratin in pangolin scales, for example, takes on a wavy pattern that makes the scales hard to crack. Peafowl feathers, meanwhile, are made up of melanin rods embedded in a matrix of keratin, which allows these adornments to be both colorful and stiff at the same time—perfect for peacocks that want to spread their tail feathers.

“One of the biggest things we can learn from nature is how these materials exhibit multiple functions that work together in perfect synergy,” Nepal said.

From atoms up

Making advanced synthetic materials with multiple functions in the lab, however, can get tricky.

“Most of current human-made materials are simple, single-component materials with simplistic uniform morphology and composition,” Tsukruk said. “And what we learnt from nature is that much more complex and sustainable organization is required to make new bio-inspired materials for advanced applications in the near future.”

One of the biggest challenges, Heinz said, comes down to models. His research group uses these tools to simulate new kinds of materials at the scale of a few hundred to millions of atoms. But taking those kinds of tiny designs and scaling them up to the size of something you can actually see becomes an increasingly difficult task.

“From the scale of atoms to the millimeter or even centimeter scale, there are so many levels of organization in natural materials,” Heinz said.

Heinz noted that NASA has recently invested in exploring hierarchically-engineered materials for aerospace applications—such as stronger and more lightweight panels of nanostructured carbon for use in spacecraft to carry life supplies to Mars. Heinz, for example, is part of a $15 million effort funded by NASA to study these kinds of “ultrastrong composites.”

Engineers, he added, are also discovering new ways to make nanocomposites in large quantities in a manufacturing setting. Today, researchers often use tools like 3D printers to make these materials, laying them down drop by drop.

Heinz, Tsukruk, Nepal, and their colleagues are optimistic. Nature, they report, has had millions of years to learn how to construct materials like pangolin scales or oyster nacre as efficiently as possible. Engineers may be able to take clues from pangolins and oysters to build materials without creating a lot of harmful waste in the process.

“If we learn from nature, we can find alternatives to many current energy-intensive manufacturing processes or hazardous chemicals,” Heinz said.

Krishan Kanhaiya, a recent PhD graduate in chemical and biological engineering at CU Boulder, also served as a co-author on the new study. Other co-authors include researchers from Georgia Institute of Technology; Carnegie Mellon University; Duke University; MIT; University College London; Johns Hopkins University; Deakin University; Tufts University; University of Michigan; University of Cambridge; University of Oxford; University of California San Diego; and Rice University.

A crystal shape conundrum is finally solved

Rice theorists’ method can predict shapes of crystals that lack symmetry

Peer-Reviewed Publication

RICE UNIVERSITY

SHAPES 1 

IMAGE: RICE UNIVERSITY RESEARCHERS HAVE DEVELOPED A METHOD TO PREDICT HOW CRYSTALS TAKE SHAPE FROM THEIR INTERNAL CHEMISTRY, EVEN WHEN THE CRYSTAL LACKS SYMMETRY. THIS REPRESENTATION OF A SILVER NITRATE CRYSTAL HAS EIGHT EDGES, NONE OF WHICH MATCH THE OTHERS. THE RICE TEAM’S ALGORITHM WAS STILL ABLE TO PREDICT ITS SHAPE. view more 

CREDIT: ILLUSTRATION BY LUQING WANG/RICE UNIVERSITY

HOUSTON – (Nov. 28, 2022) – A crystal’s shape is determined by its inherent chemistry, a characteristic that ultimately determines its final form from the most basic of details. But sometimes the lack of symmetry in a crystal makes the surface energies of its facets unknowable, confounding any theoretical prediction of its shape.

Theorists at Rice University say they’ve found a way around this conundrum by assigning arbitrary latent energies to its surfaces or, in the case of two-dimensional materials, its edges.

Yes, it seems like cheating, but in the same way a magician finds a select card in a deck by narrowing the possibilities, a little algebraic sleight-of-hand goes a long way to solve the problem of predicting a crystal’s shape.

The method described in Nature Computational Science shows using what they call auxiliary edge energies can bring predictions back in line with the Wulff construction, a geometrical recipe in use for more than a century to determine how crystals arrive at their final equilibrium shapes.

The open-access paper by materials physicist Boris Yakobson, lead author and alumnus Luqing Wang and their colleagues at Rice’s George R. Brown School of Engineering introduces algorithms that employ arbitrary numbers for the right-hand factors in the equations and still deliver the proper unique shape-solution. 

“The issue of shape is compelling, but researchers have been trying and failing for years to compute surface energies for asymmetrical crystals,” Yakobson said. “It turns out we were falling down a rabbit hole, but we knew that if nature can find a solution through a gazillion atomic movements, there should also be a way for us to determine it.”

He said the rise of interest in 2D materials in recent times motivated the new study. “We had a ‘eureka’ moment: After switching our geometrical thinking to algebraic we added closure equations that contain arbitrary parameters,” Yakobson said. “These seem useless, but we passed it all through the computer and observed a well-defined shape coming out,” he said. 

“The hard part was convincing our reviewers that edge energy is truly undefinable, but a solution can still be achieved,” Wang said.

The work could provide a valuable tool to researchers who grow crystals from the bottom up for catalytic, light-emitting, sensing, magnetic and plasmonic applications, especially when their shapes and active edges are of particular importance. 

The researchers pointed out that natural crystals enjoy the luxury of geological time. They arrive at their shapes by “relentlessly performing a trial-and-error experiment” as they seek equilibrium, the minimal energy of all their constituent atoms. 

But computational and theoretical approaches simply can’t deal with billions of atoms at once, so they generally lean on the energies of outward-facing atoms. For many crystals that have equivalent facets or edges, that works just fine.

In 2D materials, essentially all of the atoms are “outward-facing.” When their edges are equivalent by symmetry — in rectangles, for instance — completing a Wulff construction is simple after calculating the edge energies via density functional theory.

But in the absence of symmetry, when all the edges are different, the calculated average energy is meaningless, Yakobson said. 

“Nature has the answer to shape a crystal regardless of what it ‘knows’ or doesn’t about the edge energies,” he said. “So there is an answer. Our challenge was to mimic it with theory.”

The first step toward a solution was to consciously give up on finding the unknowable absolute edge energies and deal instead with their well-defined computable combinations, Yakobson said. Geometrically, this was quite a riddle, and for asymmetric bulk materials was hopelessly complicated. 

“But 2D materials and their planar polygons made solving the problem easier to think about than having to deal with multifaceted polyhedra,” he said.

Finding and establishing average energies was just the first step, followed by “closure equations” that used arbitrary latent material energy for the right-hand side of the equation. Even if the latter numbers were intentionally incorrect, applying all to the textbook Wulff construction resulted in the correct crystal shape.

The group tested its theory on several 2D crystals and compared the results to the crystals’ observed final forms. Their versatile equations successfully predicted the shapes, shown experimentally, of the truncated rectangle formed by 2D tin selenide, a promising thermo- and piezoelectric material, and the asymmetric needles formed by silver nitrite

Rice alumni Sharmila Shirodkar and Zhuhua Zhang are co-authors of the paper. The work was primarily supported by the Department of Energy and the Basic Energy Sciences program (DE-SC0012547) and in part by the Army Research Office Electronics Division (W911NF-16-1-0255).

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Read the paper at www.doi.org/10.1038/s43588-022-00347-5.

This news release can be found online at https://news.rice.edu/news/2022/crystal-shape-conundrum-finally-solved.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Related materials:

Yakobson Research Group: http://biygroup.blogs.rice.edu

Department of Materials Science and NanoEngineering: https://msne.rice.edu

George R. Brown School of Engineering: https://engineering.rice.edu

Image for download:

https://news-network.rice.edu/news/files/2022/11/1205_SHAPES-1-WEB.jpg

Rice University scientists have developed a method to predict how crystals take shape from their internal chemistry, even when the crystal lacks symmetry. This representation of a silver nitrate crystal has eight edges, none of which match the others. The Rice team’s algorithm was still able to predict its shape. (Credit: Illustration by Luqing Wang/Rice University)

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