Imagine you’re back in elementary school. Upon hearing the recess bell, you leave your pencils and books, and rush outside to the alluring glint of the playground in the sunlight. You ascend the slide’s steps, but hesitate. You touch the metal surface and pull back immediately. The metal is overwhelmingly hot from sunlight exposure.
Rest assured inner child, because scientists from Johns Hopkins Univ. have developed glass paint capable of protecting buildings, naval ships and, yes, even playground equipment from brutal sun rays.
“With sunlight, you think of UV (ultraviolet) degradation and those types of things, but one of the things that I think people forget is that just the heating itself can cause a lot of damage,” said Jason J. Benkoski, of the university’s Applied Physics Laboratory. Think about “corrosion, for example. If you put corrosion inhibitors in your paint, in order to protect steel or aluminum, you’ll be happy if you can decrease the rate of corrosion by a factor of 10.”
However, direct sunlight is capable of raising surface temperatures by 30 or 40 C, which increases corrosion by a factor of 16, according to Benkoski.
Cambo Topic
Monday, August 24, 2015
Electrospray solves longstanding problem in Langmuir-Blodgett assembly
Since Langmuir-Blodgett assembly was first reported more than 80 years ago, numerous applications have been demonstrated. Yet the technique itself and the accompanying procedure have remained largely unchanged.
New, stable 2-D materials
Dozens of new 2-D materials similar to graphene are now available, thanks to research from Univ. of Manchester scientists.
These 2-D crystals are capable of delivering designer materials with revolutionary new properties.
The problem has been that the vast majority of these atomically thin 2-D crystals are unstable in air, so react and decompose before their properties can be determined and their potential applications investigated.
Writing in NanoLetters, the Univ. of Manchester team demonstrate how tailored fabrication methods can make these previously inaccessible materials useful.
By protecting the new reactive crystals with more stable 2-D materials, such as graphene, via computer control in a specially designed inert gas chamber environments, these materials can be successfully isolated to a single atomic layer for the first time.
Combining a range of 2-D materials in thin stacks give scientists the opportunity to control the properties of the materials, which can allow “materials-to-order” to meet the demands of industry.
High-frequency electronics for satellite communications, and lightweight batteries for mobile energy storage are just two of the application areas that could benefit from this research. The breakthrough could allow for many more atomically thin materials to be studied separately as well as serve as building blocks for multilayer devices with such tailored properties.
The team, led by Dr. Roman Gorbachev, used their unique fabrication method on two particular 2-D crystals that have generated intense scientific interest in the past 12 months but are unstable in air: black phosphorus and niobium diselenide.
The technique the team have pioneered allows the unique characteristics and excellent electronic properties of these air-sensitive 2-D crystals to be revealed for the first time.
The isolation of graphene in 2004 by a Univ. of Manchester team lead by Sir Andre Geim and Sir Kostya Novoselov led to the discovery of a range of 2-D materials, each with specific properties and qualities.
Dr. Gorbachev said: “This is an important breakthrough in the area of 2-D materials research, as it allows us to dramatically increase the variety of materials that we can experiment with using our expanding 2-D crystal toolbox.
“The more materials we have to play with, the greater potential there is for creating applications that could revolutionize the way we live.” Sir Andre Geim added.
These 2-D crystals are capable of delivering designer materials with revolutionary new properties.
The problem has been that the vast majority of these atomically thin 2-D crystals are unstable in air, so react and decompose before their properties can be determined and their potential applications investigated.
Writing in NanoLetters, the Univ. of Manchester team demonstrate how tailored fabrication methods can make these previously inaccessible materials useful.
By protecting the new reactive crystals with more stable 2-D materials, such as graphene, via computer control in a specially designed inert gas chamber environments, these materials can be successfully isolated to a single atomic layer for the first time.
Combining a range of 2-D materials in thin stacks give scientists the opportunity to control the properties of the materials, which can allow “materials-to-order” to meet the demands of industry.
High-frequency electronics for satellite communications, and lightweight batteries for mobile energy storage are just two of the application areas that could benefit from this research. The breakthrough could allow for many more atomically thin materials to be studied separately as well as serve as building blocks for multilayer devices with such tailored properties.
The team, led by Dr. Roman Gorbachev, used their unique fabrication method on two particular 2-D crystals that have generated intense scientific interest in the past 12 months but are unstable in air: black phosphorus and niobium diselenide.
The technique the team have pioneered allows the unique characteristics and excellent electronic properties of these air-sensitive 2-D crystals to be revealed for the first time.
The isolation of graphene in 2004 by a Univ. of Manchester team lead by Sir Andre Geim and Sir Kostya Novoselov led to the discovery of a range of 2-D materials, each with specific properties and qualities.
Dr. Gorbachev said: “This is an important breakthrough in the area of 2-D materials research, as it allows us to dramatically increase the variety of materials that we can experiment with using our expanding 2-D crystal toolbox.
“The more materials we have to play with, the greater potential there is for creating applications that could revolutionize the way we live.” Sir Andre Geim added.
Detecting Brain Injury with Colors
In 2014, PBS reported researchers found 76 of 79 deceased NFL players showed signs of a degenerative brain disease called chronic traumatic encephalopathy.
The disease, according to Boston Univ., is associated with “repetitive brain trauma, including symptomatic concussions, as well as asymptomatic subconcussive hits to the head.” It can manifest years, and even decades, after the last hit to the head. Symptoms include memory loss, confusion, impaired judgment, aggression, depression and progressive dementia.
Head trauma is causing brain damage to athletes and soldiers in the battlefield, said Shu Yang, of the Univ. of Pennsylvania. But how does one know a hit to the head warrants a trip to the hospital?
Yang’s research team, which includes colleagues from Villanova Univ. and Temple Univ., has developed a polymer-based patch capable of changing color depending on how hard it’s hit. Ideally, multiple patches would be applied to a helmet, allowing it to detect force from multiple angles.
Yang presented her team’s research at the 250 National Meeting & Exposition of the American Chemical Society.
According to Yang, finding brain trauma initially after a hit is difficult. Athletes and soldiers may continue their physically intensive activities without knowledge of being injured. But “using this patch, we can now detect the force of the hit,” she said.
Using holographic lithography, the research team initially created photonic crystals intentionally designed a certain color. The substance changed color when applied force deformed its internal structure. But the photonic crystal route was too expensive for mass scale production.
The team turned to polymer-based materials, finding inspiration in opal formed from silicone beads. The material ended up behaving much like the specialized photonic crystals. “To make a mold, the researchers mixed up silica particles of various sizes and allowed them to self-assemble into crystals with the desired pattern,” according to the American Chemical Society. “They heated the polymer, which infiltrated the mold, allowed it to solidify and then removed the silica mold, leaving behind the inversed polymer crystals.”
The polymer used is SU-8, a photoresist invented by IBM, Yang said.
According to the team, applying 30 mN force, equivalent to a sedan crashing into a brick wall at 80 mph, caused the material to change from red to green. A 90 mN force changed the material to purple.
The team still needs to build a correlation between color change and brain injury. A simple change of color isn’t indicative of head trauma. Yang said the team plans to work with medical practitioners to build a correlation scheme.
The disease, according to Boston Univ., is associated with “repetitive brain trauma, including symptomatic concussions, as well as asymptomatic subconcussive hits to the head.” It can manifest years, and even decades, after the last hit to the head. Symptoms include memory loss, confusion, impaired judgment, aggression, depression and progressive dementia.
Head trauma is causing brain damage to athletes and soldiers in the battlefield, said Shu Yang, of the Univ. of Pennsylvania. But how does one know a hit to the head warrants a trip to the hospital?
Yang’s research team, which includes colleagues from Villanova Univ. and Temple Univ., has developed a polymer-based patch capable of changing color depending on how hard it’s hit. Ideally, multiple patches would be applied to a helmet, allowing it to detect force from multiple angles.
Yang presented her team’s research at the 250 National Meeting & Exposition of the American Chemical Society.
According to Yang, finding brain trauma initially after a hit is difficult. Athletes and soldiers may continue their physically intensive activities without knowledge of being injured. But “using this patch, we can now detect the force of the hit,” she said.
Using holographic lithography, the research team initially created photonic crystals intentionally designed a certain color. The substance changed color when applied force deformed its internal structure. But the photonic crystal route was too expensive for mass scale production.
The team turned to polymer-based materials, finding inspiration in opal formed from silicone beads. The material ended up behaving much like the specialized photonic crystals. “To make a mold, the researchers mixed up silica particles of various sizes and allowed them to self-assemble into crystals with the desired pattern,” according to the American Chemical Society. “They heated the polymer, which infiltrated the mold, allowed it to solidify and then removed the silica mold, leaving behind the inversed polymer crystals.”
The polymer used is SU-8, a photoresist invented by IBM, Yang said.
According to the team, applying 30 mN force, equivalent to a sedan crashing into a brick wall at 80 mph, caused the material to change from red to green. A 90 mN force changed the material to purple.
The team still needs to build a correlation between color change and brain injury. A simple change of color isn’t indicative of head trauma. Yang said the team plans to work with medical practitioners to build a correlation scheme.
Using nanoscopic pores to investigate protein structure
Univ. of Pennsylvania researchers have made strides toward a new method of gene sequencing a strand of DNA’s bases are read as they are threaded through a nanoscopic hole.
In a new study, they have shown that this technique can also be applied to proteins as way to learn more about their structure.
Existing methods for this kind of analysis are labor intensive, typically entailing the collection of large quantities of the protein. They also often require modifying the protein, limiting these methods’ usefulness for understanding the protein’s behavior in its natural state.
The Penn State Univ. researchers’ translocation technique allows for the study of individual proteins without modifying them. Samples taken from a single individual could be analyzed this way, opening applications for disease diagnostics and research.
The study was led by Marija Drndić, a professor in the School of Arts & Sciences’ Dept. of Physics & Astronomy; David Niedzwiecki, a postdoctoral researcher in her lab; and Jeffery G. Saven, a professor in Penn Arts & Sciences’ Dept. of Chemistry.
It was published in ACS Nano.
The Penn team’s technique stems from Drndić’s work on nanopore gene sequencing, which aims to distinguish the bases in a strand of DNA by the different percent of the aperture they each block as they pass through a nanoscopic pore. Different silhouettes allow different amounts of an ionic liquid to pass through. The change in ion flow is measured by electronics surrounding the pore; the peaks and valleys of that signal can be correlated to each base.
While researchers work to increase the accuracy of these readings to useful levels, Drndić and her colleagues have experimented with applying the technique to other biological molecules and nanoscale structures.
Collaborating with Saven’s group, they set out to test their pores on even trickier biological molecules.
“There are many proteins that are much smaller and harder to manipulate than a strand of DNA that we’d like to study,” Saven said. “We’re interested in learning about the structure of a given protein, such as whether it exists as a monomer, or combined with another copy into a dimer, or an aggregate of multiple copies known as an oligomer.”
Detection is also often a limitation.
“There are no ways to amplify peptides and proteins like there are for DNA,” Drndić said. “If you want to study proteins from a particular source, you're stuck with very small samples. With this method, however, you can just collect the amount of data you need and the number of proteins you want to pass through the pore and then study them one at a time as they naturally exist in the body.”
Using the Drndić group’s silicon nitride nanopores, which can be drilled to custom diameters, the research team set out to test their technique on GCN4-p1, a protein selected because it contains a common structural motif found in transcription factors and intracellular receptors.
“The dimer version is ‘zipped’ together,” Niedzwiecki said, “It is a ‘coiled coil’ of interleaved helices that is roughly cylindrical. The monomer version is unzipped and is likely not helical; it’s probably more like a string.”
The researchers put different ratios of zipped and unzipped versions of the protein in an ionic fluid and passed them through the pores. While unable to tell the difference between individual proteins, the researchers could perform this analysis on populations of the molecule.
“The dimer and monomer form of the protein block a different number of ions, so we see a different drop in current when they go through the pore,” Niedzwiecki said. “But we get a range of values for both, as not every molecular translocation event is the same.”
Determining whether a specific sample of these types of proteins are aggregating or not could be used to better understand the progression of disease.
“Many researchers,” Saven said, “have observed these long tangles of aggregated peptides and proteins in diseases like Alzheimer’s and Parkinson’s, but there is an increasing body of evidence that is suggesting these tangles are occurring after the fact, that what are really causing the problem are smaller protein assemblies. Figuring out what those assemblies are and how large they are is currently really hard to do, so this may be a way of solving that problem.”
In a new study, they have shown that this technique can also be applied to proteins as way to learn more about their structure.
Existing methods for this kind of analysis are labor intensive, typically entailing the collection of large quantities of the protein. They also often require modifying the protein, limiting these methods’ usefulness for understanding the protein’s behavior in its natural state.
The Penn State Univ. researchers’ translocation technique allows for the study of individual proteins without modifying them. Samples taken from a single individual could be analyzed this way, opening applications for disease diagnostics and research.
The study was led by Marija Drndić, a professor in the School of Arts & Sciences’ Dept. of Physics & Astronomy; David Niedzwiecki, a postdoctoral researcher in her lab; and Jeffery G. Saven, a professor in Penn Arts & Sciences’ Dept. of Chemistry.
It was published in ACS Nano.
The Penn team’s technique stems from Drndić’s work on nanopore gene sequencing, which aims to distinguish the bases in a strand of DNA by the different percent of the aperture they each block as they pass through a nanoscopic pore. Different silhouettes allow different amounts of an ionic liquid to pass through. The change in ion flow is measured by electronics surrounding the pore; the peaks and valleys of that signal can be correlated to each base.
While researchers work to increase the accuracy of these readings to useful levels, Drndić and her colleagues have experimented with applying the technique to other biological molecules and nanoscale structures.
Collaborating with Saven’s group, they set out to test their pores on even trickier biological molecules.
“There are many proteins that are much smaller and harder to manipulate than a strand of DNA that we’d like to study,” Saven said. “We’re interested in learning about the structure of a given protein, such as whether it exists as a monomer, or combined with another copy into a dimer, or an aggregate of multiple copies known as an oligomer.”
Detection is also often a limitation.
“There are no ways to amplify peptides and proteins like there are for DNA,” Drndić said. “If you want to study proteins from a particular source, you're stuck with very small samples. With this method, however, you can just collect the amount of data you need and the number of proteins you want to pass through the pore and then study them one at a time as they naturally exist in the body.”
Using the Drndić group’s silicon nitride nanopores, which can be drilled to custom diameters, the research team set out to test their technique on GCN4-p1, a protein selected because it contains a common structural motif found in transcription factors and intracellular receptors.
“The dimer version is ‘zipped’ together,” Niedzwiecki said, “It is a ‘coiled coil’ of interleaved helices that is roughly cylindrical. The monomer version is unzipped and is likely not helical; it’s probably more like a string.”
The researchers put different ratios of zipped and unzipped versions of the protein in an ionic fluid and passed them through the pores. While unable to tell the difference between individual proteins, the researchers could perform this analysis on populations of the molecule.
“The dimer and monomer form of the protein block a different number of ions, so we see a different drop in current when they go through the pore,” Niedzwiecki said. “But we get a range of values for both, as not every molecular translocation event is the same.”
Determining whether a specific sample of these types of proteins are aggregating or not could be used to better understand the progression of disease.
“Many researchers,” Saven said, “have observed these long tangles of aggregated peptides and proteins in diseases like Alzheimer’s and Parkinson’s, but there is an increasing body of evidence that is suggesting these tangles are occurring after the fact, that what are really causing the problem are smaller protein assemblies. Figuring out what those assemblies are and how large they are is currently really hard to do, so this may be a way of solving that problem.”
Nanocrystals don’t add up for reactor materials
Lawrence Livermore National Laboratory researchers have found that nanocrystalline materials don’t necessarily resist radiation effects in nuclear reactors better than currently used materials.
As researchers hunt for materials with the ability to withstand prolonged radiation damage, the use of nanostructured materials, with high interfacial area to absorb radiation-induced defects, has been considered as an enabling technology for future reactor designs and longer-lasting reactor components. For years, simulations had shown that nanocrystals would not only absorb radiation damage better than the polycrystalline materials used in nuclear reactors today, but they also would be functional at the elevated temperatures in those reactors.
However, earlier research published in Applied Physics Letters by Mukul Kumar and his LLNL colleagues, showed through experiments that nanocrystalline materials have poor stability under the thermal conditions in reactors. And in new research, published in Acta Materialia, Kumar’s team, through extensive in-situ high-voltage transmission electron microscopy (TEM), have discovered that the nanocrystalline materials do not survive radiation damage either.
Most structural materials used in nuclear reactors are prone to radiation damage that degrade their mechanical properties and limit their service life. High-energy particle irradiation produces defects in these materials that are mobile at high temperatures and are influenced by stress fields associated with pre-existing extended defects. After an initial relaxation phase, the defects that do not recombine aggregate to produce defect clusters or diffuse rapidly to interfaces and other defects, inducing detrimental microstructural evolution
Scientists have been searching for years to find new material for components within nuclear reactors that could better withstand high temperatures and radiation damage. Current materials last between four to five years before they are swapped out for new ones. Kumar said initially his team thought the nanostructures, particularly with a high density of low energy interfaces such as twin boundaries thought to arrest thermal coarsening, would be able to extend the lifetime of those components up to 25 years.
But the experimental results showed differently. “We’ve shown why it doesn’t work,” he said. The team supposed that a high density grain boundary area would act as an effective sink for radiation-induced defects. However, continued absorption of defects can alter the structure of grain boundaries and/or enhance their mobility, eventually leading to microstructural degradation in the form of grain coarsening, thus negating their initial radiation tolerance.
The final results showed the nanocrystals did not survive radiation damage any better than the currently used materials.
However, Kumar said a new kind of grain boundary network could be engineered in polycrystalline microstructures (with micron-scale grains) that might better withstand high temperatures, resist radiation damage and extend the lifetime of reactor components. Such a network, appropriately coordinated, would comprise of a mix of low energy boundaries to resist thermal coarsening and high-energy boundaries to absorb the defects.
As researchers hunt for materials with the ability to withstand prolonged radiation damage, the use of nanostructured materials, with high interfacial area to absorb radiation-induced defects, has been considered as an enabling technology for future reactor designs and longer-lasting reactor components. For years, simulations had shown that nanocrystals would not only absorb radiation damage better than the polycrystalline materials used in nuclear reactors today, but they also would be functional at the elevated temperatures in those reactors.
However, earlier research published in Applied Physics Letters by Mukul Kumar and his LLNL colleagues, showed through experiments that nanocrystalline materials have poor stability under the thermal conditions in reactors. And in new research, published in Acta Materialia, Kumar’s team, through extensive in-situ high-voltage transmission electron microscopy (TEM), have discovered that the nanocrystalline materials do not survive radiation damage either.
Most structural materials used in nuclear reactors are prone to radiation damage that degrade their mechanical properties and limit their service life. High-energy particle irradiation produces defects in these materials that are mobile at high temperatures and are influenced by stress fields associated with pre-existing extended defects. After an initial relaxation phase, the defects that do not recombine aggregate to produce defect clusters or diffuse rapidly to interfaces and other defects, inducing detrimental microstructural evolution
Scientists have been searching for years to find new material for components within nuclear reactors that could better withstand high temperatures and radiation damage. Current materials last between four to five years before they are swapped out for new ones. Kumar said initially his team thought the nanostructures, particularly with a high density of low energy interfaces such as twin boundaries thought to arrest thermal coarsening, would be able to extend the lifetime of those components up to 25 years.
But the experimental results showed differently. “We’ve shown why it doesn’t work,” he said. The team supposed that a high density grain boundary area would act as an effective sink for radiation-induced defects. However, continued absorption of defects can alter the structure of grain boundaries and/or enhance their mobility, eventually leading to microstructural degradation in the form of grain coarsening, thus negating their initial radiation tolerance.
The final results showed the nanocrystals did not survive radiation damage any better than the currently used materials.
However, Kumar said a new kind of grain boundary network could be engineered in polycrystalline microstructures (with micron-scale grains) that might better withstand high temperatures, resist radiation damage and extend the lifetime of reactor components. Such a network, appropriately coordinated, would comprise of a mix of low energy boundaries to resist thermal coarsening and high-energy boundaries to absorb the defects.
Engineered hot fat implants reduce weight gain in mice
Scientists at the Univ. of California, Berkeley (UC Berkeley) have developed a novel way to engineer the growth and expansion of energy-burning “good” fat, and then found that this fat helped reduce weight gain and lower blood glucose levels in mice.
The authors of the study, published in Diabetes, said their technique could eventually lead to new approaches to combat obesity, diabetes and other metabolic disorders.
The researchers used a specifically tailored hydrogel to “scaffold” and control an implant containing stem cells to form a functional brown-fat-like tissue. While white fat—the kind associated with obesity—stores excess energy, brown fat serves as a heat generator, burning calories as it does its job.
“What is truly exciting about this system is its potential to provide plentiful supplies of brown fat for therapeutic purposes,” said study lead author Kevin Tharp, a PhD student in the Dept. of Nutritional Sciences and Toxicology. “The implant is made from the stem cells that reside in white fat, which could be made from tissue obtained through liposuction.”
Human babies, which cannot yet produce heat by shivering, have greater stores of brown fat, so-called because it contains high levels of darker-hued mitochondria. It was once believed that brown fat disappears with age, but in recent years, this tissue has been discovered in the neck, shoulders, and spinal cord among adults.
“This is figuratively and literally a hot area of research right now,” said the study’s senior author, Andreas Stahl, an associate professor of nutritional sciences and toxicology. “We are the first to implant in mice an artificial brown-fat depot and show that it has the expected effects on body temperature and beneficial effects on metabolism.”
Studies have shown that cold temperatures can bump up activity in brown fat. Stahl noted, however, that the exposure to cold often led to increases in food intake, as well, potentially negating any calorie-burning benefits from brown-fat activity.
Get the fat, not the cold
There are three basic types of fat tissue in our bodies. There is the classic, energy-storing white fat that many of us are most familiar with, and two kinds of energy-burning fat used to generate heat, namely brown fat, which arises during fetal development, and beige fat, which is brown-like fat formed within white fat tissue after exposure to cold and other situations.
This UC Berkeley experiment explored the idea of increasing brown-like beige fat without the temperature drop. Stahl teamed up with Kevin Healy, UC Berkeley professor of bioengineering, and postdoctoral researcher Amit Jha to develop a system of physical cues to guide stem cell differentiation.
“It’s already known that for a number of organs, including the heart, the extracellular matrix in which a cell resides provides signals to guide growth and development,” said Healy, who also has an appointment in the Dept. of Materials Science and Engineering. “We applied this concept to stem cells isolated from white-fat tissue.”
The specific matrix recipe for converting white-fat stem cells to brown fat had been unclear, the researchers said, but they noted that previous studies suggested that stiffness of the surrounding environment was a factor. White-fat stem cells placed in a 3-D environment that is soft, with little resistance as the cell grows, became fat. When the surrounding environment was very stiff, the stem cells grew into bone.
Injected brown fat reduces weight gain, glucose
The researchers created a tightly knit 3-D mesh in a hydrogel containing water, hyaluronic acid and short protein sequences associated with brown-fat growth and function. Hyaluronic acid is a naturally occurring carbohydrate that helps make water thicker and gel-like. They then took white-fat stem cells from mice genetically engineered to express an enzyme from fireflies. This made the cells luminescent, allowing the researchers to track them more easily.
The researchers then added the cells to the hydrogel and, before the mixture thickened, injected them under the skin of genetically identical mice.
The gel polymerizes after injection and completes its transformation in the animal. The researchers monitored the glowing cells after injection to determine how well they stayed put, how long they persisted in the body and whether they were metabolically functional.
They noticed an increase in the core body temperature of the mice at ambient temperatures of 21 C and after 24 hrs at a chilly 4 C. In both cases, the mice with the implanted cells were up to half a degree Celsius warmer than a control group of mice with no injection. The higher the concentration of cells, the larger the effect on temperature.
The researchers also put the experimental mice on a high-fat diet. By the end of three weeks, the mice with injected beige fat gained half as much weight and had lower levels of blood glucose and circulating fatty acids compared with control mice.
“This is a feasibility study, but the results were very encouraging,” said Stahl. “It is the first time an optimized 3-D environment has been created to stimulate the growth of brown-like fat. Given the negative health effects of obesity, research into the role of brown fat should continue to see if these findings would be effective in humans.”
The authors of the study, published in Diabetes, said their technique could eventually lead to new approaches to combat obesity, diabetes and other metabolic disorders.
The researchers used a specifically tailored hydrogel to “scaffold” and control an implant containing stem cells to form a functional brown-fat-like tissue. While white fat—the kind associated with obesity—stores excess energy, brown fat serves as a heat generator, burning calories as it does its job.
“What is truly exciting about this system is its potential to provide plentiful supplies of brown fat for therapeutic purposes,” said study lead author Kevin Tharp, a PhD student in the Dept. of Nutritional Sciences and Toxicology. “The implant is made from the stem cells that reside in white fat, which could be made from tissue obtained through liposuction.”
Human babies, which cannot yet produce heat by shivering, have greater stores of brown fat, so-called because it contains high levels of darker-hued mitochondria. It was once believed that brown fat disappears with age, but in recent years, this tissue has been discovered in the neck, shoulders, and spinal cord among adults.
“This is figuratively and literally a hot area of research right now,” said the study’s senior author, Andreas Stahl, an associate professor of nutritional sciences and toxicology. “We are the first to implant in mice an artificial brown-fat depot and show that it has the expected effects on body temperature and beneficial effects on metabolism.”
Studies have shown that cold temperatures can bump up activity in brown fat. Stahl noted, however, that the exposure to cold often led to increases in food intake, as well, potentially negating any calorie-burning benefits from brown-fat activity.
Get the fat, not the cold
There are three basic types of fat tissue in our bodies. There is the classic, energy-storing white fat that many of us are most familiar with, and two kinds of energy-burning fat used to generate heat, namely brown fat, which arises during fetal development, and beige fat, which is brown-like fat formed within white fat tissue after exposure to cold and other situations.
This UC Berkeley experiment explored the idea of increasing brown-like beige fat without the temperature drop. Stahl teamed up with Kevin Healy, UC Berkeley professor of bioengineering, and postdoctoral researcher Amit Jha to develop a system of physical cues to guide stem cell differentiation.
“It’s already known that for a number of organs, including the heart, the extracellular matrix in which a cell resides provides signals to guide growth and development,” said Healy, who also has an appointment in the Dept. of Materials Science and Engineering. “We applied this concept to stem cells isolated from white-fat tissue.”
The specific matrix recipe for converting white-fat stem cells to brown fat had been unclear, the researchers said, but they noted that previous studies suggested that stiffness of the surrounding environment was a factor. White-fat stem cells placed in a 3-D environment that is soft, with little resistance as the cell grows, became fat. When the surrounding environment was very stiff, the stem cells grew into bone.
Injected brown fat reduces weight gain, glucose
The researchers created a tightly knit 3-D mesh in a hydrogel containing water, hyaluronic acid and short protein sequences associated with brown-fat growth and function. Hyaluronic acid is a naturally occurring carbohydrate that helps make water thicker and gel-like. They then took white-fat stem cells from mice genetically engineered to express an enzyme from fireflies. This made the cells luminescent, allowing the researchers to track them more easily.
The researchers then added the cells to the hydrogel and, before the mixture thickened, injected them under the skin of genetically identical mice.
The gel polymerizes after injection and completes its transformation in the animal. The researchers monitored the glowing cells after injection to determine how well they stayed put, how long they persisted in the body and whether they were metabolically functional.
They noticed an increase in the core body temperature of the mice at ambient temperatures of 21 C and after 24 hrs at a chilly 4 C. In both cases, the mice with the implanted cells were up to half a degree Celsius warmer than a control group of mice with no injection. The higher the concentration of cells, the larger the effect on temperature.
The researchers also put the experimental mice on a high-fat diet. By the end of three weeks, the mice with injected beige fat gained half as much weight and had lower levels of blood glucose and circulating fatty acids compared with control mice.
“This is a feasibility study, but the results were very encouraging,” said Stahl. “It is the first time an optimized 3-D environment has been created to stimulate the growth of brown-like fat. Given the negative health effects of obesity, research into the role of brown fat should continue to see if these findings would be effective in humans.”
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