Molecules belonging to an almost unknown bioluminescent system found in larvae of the fungus gnat Orfelia fultoni (subfamily Keroplatinae) have been isolated for the first time by researchers at the Federal University of São Carlos (UFSCar) in the state of São Paulo, Brazil. The small fly is one of the few terrestrial organisms that produce blue light. It inhabits riverbanks in the Appalachian Mountains in the eastern United States. A key part of its bioluminescent system is a molecule also present in two recently discovered Brazilian flies.
The study, supported by Paulo Research Foundation – FAPESP, is published in Scientific Reports. Five authors are affiliated with UFSCar and two with universities in the United States.
The bioluminescent systems of glow-worms, fireflies and other insects are normally made up of luciferin (a low molecular weight molecule) and luciferase, an enzyme that catalyzes the oxidation of luciferin by oxygen, producing light. While some bioluminescent systems are well known and even used in biotechnological applications, others are poorly understood, including blue light-emitting systems, such as that of O. fultoni.
“In the published paper, we describe the properties of the insect’s luciferase and luciferin and their anatomical location in its larvae. We also specify several possible proteins that are possible candidates for the luciferase. We don’t yet know what type of protein it is, but it’s likely to be a hexamerin. In insects, hexamerins are storage proteins that provide amino acids, besides having other functions, such as binding low molecular weight compounds, like luciferin,” said Vadim Viviani, a professor in UFSCar’s Sustainability Science and Technology Center (CCTS) in Sorocaba, São Paulo, and principal investigator for the study.
The study was part of the FAPESP-funded project “Arthropod bioluminescence“. The partnership with United States-based researchers dates from a previous project, supported by FAPESP and the United States National Science Foundation (NSF), in partnership with Vanderbilt University (VU), located in Nashville, Tennessee.
In addition to luciferin and luciferase, researchers began characterizing a complex found in insects of the family Keroplatidae, which, in addition to O. fultoni, also includes a Brazilian species in the genus Neoditomyia that produces only luciferin and hence does not emit light.
Because they do not use it to emit light, the luciferin in O. fultoni and the Brazilian Neoditomyia has been named keroplatin. In larvae of this subfamily, keroplatin is associated with “black bodies” – large cells containing dark granules, proteins and probably mitochondria (energy-producing organelles). Researchers are still investigating the biological significance of this association between keroplatin and mitochondria.
“It’s a mystery,” Viviani said. “This luciferin may play a role in the mitochondrial energy metabolism. At night, probably in the presence of a natural chemical reducer, the luciferin is released by these black bodies and reacts with the surrounding luciferase to produce blue light. These are possibilities we plan to study.”
An important factor in the elucidation of the United States insect’s bioluminescent system was the discovery of a larva that lives in Intervales State Park in São Paulo in 2018. It does not emit light but produces luciferin, similar to O. fultoni (read more at: agencia.fapesp.br/29066).
In their latest study, the group injected purified luciferase from the United States species into larvae of the Brazilian species, which then produced blue light. The nonluminescent Brazilian species is more abundant in nature than the United States species, so a larger amount of the material could be obtained for study purposes, especially to characterize the luciferin (keroplatin) present in both species.
In 2019, the group discovered and described Neoceroplatus betaryensis, a new species of fungus gnat, in collaboration with Cassius Stevani, a professor at the University of São Paulo’s Institute of Chemistry (IQ-USP). It was the first blue light-emitting insect found in South America and was detected in a privately held forest reserve near the Upper Ribeira State Tourist Park (PETAR) in the southern portion of the state of São Paulo. A close relative of O. fultoni, N. betaryensis inhabits fallen tree trunks in humid places (read more at: agencia.fapesp.br/31797).
“We show that the bioluminescent system of this Brazilian species is identical to that of O. fultoni. However, the insect is very rare, and so it’s hard to obtain sufficient material for research purposes,” Viviani said.
The researchers are now cloning the insect’s luciferase and characterizing it in molecular terms. They are also analyzing the chemical structure of its luciferin and the morphology of its lanterns.
“Once all this has been determined, we’ll be able to synthesize the luciferin and luciferase in the lab and use these systems in a range of biotech applications, such as studying cells. This will help us understand more about human diseases, among other things,” Viviani said.
I love structural colo(u) and the first such story here was this February 7, 2013 posting, which is where you’ll find the image below,
Those berries are stunning especially when you realize they are part of a long-dead Pollia plant. Scientist, Rox Middleton of University of Bristol (UK) was studying the structures that render the Pollia plant’s berries (fruit) blue when she decided to study another, more conveniently accessible plant with blue fruit. That’s when she got a surprise (from an August 11, 2020 article by Véronique Greenwood for the New York Times),
Big, leafy viburnum bushes have lined yards in the United States and Europe for decades — their domes of blossoms have an understated attractiveness. But once the flowers of the Viburnum tinus plant fade, the shrub makes something unusual: shiny, brilliantly blue fruit.
Scientists had noticed that pigments related to those in blueberries exist in viburnum fruit, and assumed that this must be the source of their odd hue. Blue fruit, after all, is rare. But researchers reported last week in Current Biology that viburnum’s blue is actually created by layers of molecules arranged under the surface of the skin, a form of what scientists call structural color. By means still unknown, the plant’s cells create thin slabs of fat [emphasis mine] arranged in a stack, like the flakes of puff pastry, and their peculiar gleam is the result.
Rox Middleton, a researcher at University of Bristol in England and an author of the new paper, had been studying the African pollia plant, which produces its own exotic blue fruit. But viburnum fruit were everywhere, and she realized that their blue had not been well-studied. Along with Miranda Sinnott-Armstrong, a researcher at the University of Colorado, Boulder, and other colleagues, she set out to take a closer look at the fruit’s skin.
The pollia fruit’s blue is a form of structural color, in which light bounces off a regularly spaced arrangement of tiny structures such that certain wavelengths, usually those that look blue or green to us, are reflected back at the viewer. In pollia fruit, the color comes from light interacting with thin sheets of cellulose packed together. At first the team thought there would be something similar in viburnum. But they saw no cellulose stacks.
The research team has concluded that all it comes down the arrangement of fat molecules, which are also responsible for the cloudier, metallic blue in viburnum berries,
According to an August 4, 2020 news item on ScienceDaily the ‘Ice-phobic’ properties of moths’ eyes have inspired a new technology,
Researchers have been working for decades on improving the anti-icing performance of functional surfaces. Ice accumulation on aircraft wings, for instance, can reduce lifting force, block moving parts and cause disastrous problems.
Research in the journal AIP [American Institute of Physics] Advances, from AIP Publishing, investigates a unique nanostructure, modeled on moth eyes, that has anti-icing properties. Moth eyes are of interest because they have a distinct ice-phobic and transparent surface.
The researchers fabricated the moth eye nanostructure on a quartz substrate that was covered with a paraffin layer to isolate it from a cold and humid environment. Paraffin wax was chosen as a coating material due to its low thermal conductivity, easy coating and original water repellency.
“We evaluated the anti-icing properties of this unique nanostructure covered with paraffin in terms of adhesion strength, freezing time and mimicking rain sustainability,” said Nguyen Ba Duc, one of the authors.
Ice accumulation on energy transmission systems, vehicles and ships in a harsh environment often leads to massive destruction and contributes to serious accidents.
The researchers found the moth eyes nanostructure surface coated in paraffin exhibited greatly improved anti-icing performance, indicating the advantage of combining original water repellency and a unique heat-delaying structure. The paraffin interfered in the icing process in both water droplet and freezing rain experiments.
The number of air blocks trapped inside the nanostructure also contributed to delaying heat transfer, leading to an increase in freezing time of the attached water droplets.
“We also determined this unique nanostructure sample is suitable for optical applications, such as eyeglasses, as it has high transparency and anti-reflective properties,” said Ba Duc.
The high transparency and anti-reflective effects were due to the nanostructure being modeled on moth eyes, which have these transparent and anti-reflective properties.
Today [May 29, 2019], PBS KIDS announced the animated series ELINOR WONDERS WHY, set to premiere Labor Day [September 7] 2020. ELINOR WONDERS WHY aims to encourage children to follow their curiosity, ask questions when they don’t understand and find answers using science inquiry skills. The main character Elinor, the most observant and curious bunny rabbit in Animal Town, will introduce kids ages 3-5 to science, nature and community through adventures with her friends. This new multiplatform series, created by Jorge Cham and Daniel Whiteson and produced in partnership with Pipeline Studios, will debut nationwide on PBS stations, the PBS KIDS 24/7 channel and PBS KIDS digital platforms.
The stories in ELINOR WONDERS WHY center around Elinor and her friends Ari, a funny and imaginative bat, and Olive, a perceptive and warm elephant. As kids explore Animal Town, they will meet all kinds of interesting, funny, and quirky characters, each with something to teach us about respecting others, the importance of diversity, caring for the environment, and working together to solve problems. In each episode, Elinor models the foundational practices of science inquiry and engineering design — including her amazing powers of observation and willingness to ask questions and investigate. When she encounters something she doesn’t understand, like why birds have feathers or how tiny ants build massive anthills, she just can’t let it go until she figures it out. And in discovering the answers, Elinor often learns something about nature’s ingenious inventions and how they can connect to ideas in our designed world, and what it takes to live in a community. ELINOR WONDERS WHY encourages children and parents to ask their own questions and experience the joy of discovery and understanding together.
Elinor Wonders Why is a STEM [science, technology, engineering, and mathematics]-based cartoon series created by Daniel Whiteson, a physicist and astronomer, and Jorge Cham, a cartoonist and robotics engineer. They’re both parents of small children, so they understand how to encourage curiosity through science and how to break down complex concepts.
Cham and Whiteson have been partners for years, working together on PhD Comics, which is a webcomic, YouTube, and podcast universe dedicated to PhD student humor. Linda Simensky, head of content for PBS Kids, had been a fan of their work, and when the opportunity to create a preschool science show that focuses on biomimicry came up, she figured they’d be great for the job.
“Biomimicry is basically taking things that you learn in nature and in the outdoors and in the natural world, and using them for inventions and for innovation science,” says Simensky. “The classic example that they use in the pilot is how Velcro was designed. Basically, it was inspired by someone getting burdock stuck to his pants, and that’s what inspired Velcro, so that’s the classic example of finding something in nature that solves a problem that you need to solve in real life.”
Elinor Wonders Why centers around Elinor (named after Cham’s daughter), a curious and observant rabbit living in Animal Town who goes on various adventures. In the upcoming premiere, Elinor plays hide-and-go-seek with her friends and finds out how animals hide in nature. …
Rocque went on to interview Cham, Whiteson, and Simensky,
FC: Describe the overall process of “dumbing down” highly sophisticated content for a younger audience. Was it harder than you thought?
JC: There was definitely a learning curve, but fortunately everyone at PBS, our team of science and education specialists have been great collaborators and guides. We don’t really believe in the phrase “dumbing down.” …
DW: Something important for us was to make each episode about a single question that a real kid would have. We looked for topics that any typical kid would think, “Huh, I do wonder why that is?” The kinds of questions they might ask when they look at their own world, like, “Why do birds have feathers?” or “Why do lizards sit in the sun?” It’s also important for us that the kids in the show play an active part in finding the answers, so we pick questions that kids could answer themselves using basic scientific thinking and simple tools, simple experiments, making observations, and comparing and contrasting. This made the questions and answers accessible, and also hopefully provides a model for them to follow at home.
LS: The part of it that’s the hardest is getting everything to work for the same age group. That’s the first thing. So, when you’re doing that, you’re doing several things at a time. You’re coming up with the idea for the show and you have to make sure that you know exactly who your age group is, and in the case of Elinor, it’s kids between the ages of 3 and 6. That’s a typical preschool group, and that includes kids who are in kindergarten, and even within 3 to 6, that’s obviously a pretty big range of kids. …
PBS does have an Elinor Wonders Why website but some of the materials (videos) are restricted to viewers based in the US. As for broadcast times, check your local PBS station, should you have one.
Scientists at Washington University have created a removable wireless camera backpack for beetles and for tiny robots resembling beetles. I’m embedding a video shot by a beetle later in this post with a citation and link for the paper, near the end of this post where you’ll also find links to my other posts on insects and technology.
In the movie “Ant-Man,” the title character can shrink in size and travel by soaring on the back of an insect. Now researchers at the University of Washington have developed a tiny wireless steerable camera that can also ride aboard an insect, giving everyone a chance to see an Ant-Man view of the world.
The camera, which streams video to a smartphone at 1 to 5 frames per second, sits on a mechanical arm that can pivot 60 degrees. This allows a viewer to capture a high-resolution, panoramic shot or track a moving object while expending a minimal amount of energy. To demonstrate the versatility of this system, which weighs about 250 milligrams — about one-tenth the weight of a playing card — the team mounted it on top of live beetles and insect-sized robots.
“We have created a low-power, low-weight, wireless camera system that can capture a first-person view of what’s happening from an actual live insect or create vision for small robots,” said senior author Shyam Gollakota, a UW associate professor in the Paul G. Allen School of Computer Science & Engineering. “Vision is so important for communication and for navigation, but it’s extremely challenging to do it at such a small scale. As a result, prior to our work, wireless vision has not been possible for small robots or insects.”
Typical small cameras, such as those used in smartphones, use a lot of power to capture wide-angle, high-resolution photos, and that doesn’t work at the insect scale. While the cameras themselves are lightweight, the batteries they need to support them make the overall system too big and heavy for insects — or insect-sized robots — to lug around. So the team took a lesson from biology.
“Similar to cameras, vision in animals requires a lot of power,” said co-author Sawyer Fuller, a UW assistant professor of mechanical engineering. “It’s less of a big deal in larger creatures like humans, but flies are using 10 to 20% of their resting energy just to power their brains, most of which is devoted to visual processing. To help cut the cost, some flies have a small, high-resolution region of their compound eyes. They turn their heads to steer where they want to see with extra clarity, such as for chasing prey or a mate. This saves power over having high resolution over their entire visual field.”
To mimic an animal’s vision, the researchers used a tiny, ultra-low-power black-and-white camera that can sweep across a field of view with the help of a mechanical arm. The arm moves when the team applies a high voltage, which makes the material bend and move the camera to the desired position. Unless the team applies more power, the arm stays at that angle for about a minute before relaxing back to its original position. This is similar to how people can keep their head turned in one direction for only a short period of time before returning to a more neutral position.
“One advantage to being able to move the camera is that you can get a wide-angle view of what’s happening without consuming a huge amount of power,” said co-lead author Vikram Iyer, a UW doctoral student in electrical and computer engineering. “We can track a moving object without having to spend the energy to move a whole robot. These images are also at a higher resolution than if we used a wide-angle lens, which would create an image with the same number of pixels divided up over a much larger area.”
The camera and arm are controlled via Bluetooth from a smartphone from a distance up to 120 meters away, just a little longer than a football field.
The researchers attached their removable system to the backs of two different types of beetles — a death-feigning beetle and a Pinacate beetle. Similar beetles have been known to be able to carry loads heavier than half a gram, the researchers said.
“We made sure the beetles could still move properly when they were carrying our system,” said co-lead author Ali Najafi, a UW doctoral student in electrical and computer engineering. “They were able to navigate freely across gravel, up a slope and even climb trees.”
The beetles also lived for at least a year after the experiment ended. [emphasis mine]
“We added a small accelerometer to our system to be able to detect when the beetle moves. Then it only captures images during that time,” Iyer said. “If the camera is just continuously streaming without this accelerometer, we could record one to two hours before the battery died. With the accelerometer, we could record for six hours or more, depending on the beetle’s activity level.”
The researchers also used their camera system to design the world’s smallest terrestrial, power-autonomous robot with wireless vision. This insect-sized robot uses vibrations to move and consumes almost the same power as low-power Bluetooth radios need to operate.
The team found, however, that the vibrations shook the camera and produced distorted images. The researchers solved this issue by having the robot stop momentarily, take a picture and then resume its journey. With this strategy, the system was still able to move about 2 to 3 centimeters per second — faster than any other tiny robot that uses vibrations to move — and had a battery life of about 90 minutes.
While the team is excited about the potential for lightweight and low-power mobile cameras, the researchers acknowledge that this technology comes with a new set of privacy risks.
“As researchers we strongly believe that it’s really important to put things in the public domain so people are aware of the risks and so people can start coming up with solutions to address them,” Gollakota said.
Applications could range from biology to exploring novel environments, the researchers said. The team hopes that future versions of the camera will require even less power and be battery free, potentially solar-powered.
“This is the first time that we’ve had a first-person view from the back of a beetle while it’s walking around. There are so many questions you could explore, such as how does the beetle respond to different stimuli that it sees in the environment?” Iyer said. “But also, insects can traverse rocky environments, which is really challenging for robots to do at this scale. So this system can also help us out by letting us see or collect samples from hard-to-navigate spaces.”
Johannes James, a UW mechanical engineering doctoral student, is also a co-author on this paper. This research was funded by a Microsoft fellowship and the National Science Foundation.
I’m surprised there’s no funding from a military agency as the military and covert operation applications seem like an obvious pairing. In any event, here’s a link to and a citation for the paper,
As for my questions (how do you put the backpacks on the beetles? is there a strap, is it glue, is it something else? how heavy is the backpack and camera? how old are the beetles you use for this experiment? where did you get the beetles from? do you have your own beetle farm where you breed them?), I’ll see if I can get some answers.
A June 17, 2020 news item on Nanowerk trumpets research into how robots might be able to sport chameleon-like skin one day,
A new film made of gold nanoparticles changes color in response to any type of movement. Its unprecedented qualities could allow robots to mimic chameleons and octopi — among other futuristic applications.
Unlike other materials that try to emulate nature’s color changers, this one can respond to any type of movement, like bending or twisting. Robots coated in it could enter spaces that might be dangerous or impossible for humans, and offer information just based on the way they look.
For example, a camouflaged robot could enter tough-to-access underwater crevices. If the robot changes color, biologists could learn about the pressures facing animals that live in these environments.
Although some other color-changing materials can also respond to motion, this one can be printed and programmed to display different, complex patterns that are difficult to replicate.
This video from the University of California at Riverside researchers shows the material in action (Note: It gets more interesting after the first 20 secs.),
Nanomaterials are simply materials that have been reduced to an extremely small scale — tens of nanometers in width and length, or, about the size of a virus. When materials like silver or gold become smaller, their colors will change depending on their size, shape, and the direction they face.
“In our case, we reduced gold to nano-sized rods. We knew that if we could make the rods point in a particular direction, we could control their color,” said chemistry professor Yadong Yin. “Facing one way, they might appear red. Move them 45 degrees, and they change to green.”
The problem facing the research team was how to take millions of gold nanorods floating in a liquid solution and get them all to point in the same direction to display a uniform color.
Their solution was to fuse smaller magnetic nanorods onto the larger gold ones. The two different-sized rods were encapsulated in a polymer shield, so that they would remain side by side. That way, the orientation of both rods could be controlled by magnets.
“Just like if you hold a magnet over a pile of needles, they all point in the same direction. That’s how we control the color,” Yin said.
Once the nanorods are dried into a thin film, their orientation is fixed in place and they no longer respond to magnets. “But, if the film is flexible, you can bend and rotate it, and will still see different colors as the orientation changes,” Yin said.
Other materials, like butterfly wings, are shiny and colorful at certain angles, and can also change color when viewed at other angles. However, those materials rely on precisely ordered microstructures, which are difficult and expensive to make for large areas. But this new film can be made to coat the surface of any sized object just as easily as applying spray paint on a house.
Though futuristic robots are an ultimate application of this film, it can be used in many other ways. UC Riverside chemist Zhiwei Li, the first author on this paper, explained that the film can be incorporated into checks or cash as an authentication feature. Under normal lighting, the film is gray, but when you put on sunglasses and look at it through polarized lenses, elaborate patterns can be seen. In addition, the color contrast of the film may change dramatically if you twist the film.
The applications, in fact, are only limited by the imagination. “Artists could use this technology to create fascinating paintings that are wildly different depending on the angle from which they are viewed,” Li said. “It would be wonderful to see how the science in our work could be combined with the beauty of art.”
Scientists are working overtime to find an effective treatment for COVID-19, the illness caused by the new coronavirus, SARS-CoV-2. Many of these efforts target a specific part of the virus, such as the spike protein. Now, researchers reporting in Nano Letters have taken a different approach, using nanosponges coated with human cell membranes –– the natural targets of the virus –– to soak up SARS-CoV-2 and keep it from infecting cells in a petri dish.
To gain entry, SARS-CoV-2 uses its spike protein to bind to two known proteins on human cells, called ACE2 and CD147. Blocking these interactions would keep the virus from infecting cells, so many researchers are trying to identify drugs directed against the spike protein. Anthony Griffiths, Liangfang Zhang and colleagues had a different idea: making a nanoparticle decoy with the virus’ natural targets, including ACE2 and CD147, to lure SARS-CoV-2 away from cells. And to test this idea, they conducted experiments with the actual SARS-CoV-2 virus in a biosafety level 4 lab.
The researchers coated a nanoparticle polymer core with cell membranes from either human lung epithelial cells or macrophages –– two cell types infected by SARS-CoV-2. They showed that the nanosponges had ACE2 and CD147, as well as other cell membrane proteins, projecting outward from the polymer core. When administered to mice, the nanosponges did not show any short-term toxicity. Then, the researchers treated cells in a dish with SARS-CoV-2 and the lung epithelial or macrophage nanosponges. Both decoys neutralized SARS-CoV-2 and prevented it from infecting cells to a similar extent. The researchers plan to next test the nanosponges in animals before moving to human clinical trials. In theory, the nanosponge approach would work even if SARS-CoV-2 mutates to resist other therapies, and it could be used against other viruses, as well, the researchers say.
There are two research teams involved, one at Boston University and the other at the University of California at San Diego (UC San Diego or UCSD). The June 18, 2020 Boston University news release (also on EurekAlert) by Kat J. McAlpine adds more details about the research, provides some insights from the researchers, and is a little redundant if you’ve already seen the ACS news release,
Imagine if scientists could stop the coronavirus infection in its tracks simply by diverting its attention away from living lung cells? A new therapeutic countermeasure, announced in a Nano Letters study by researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the University of California San Diego, appears to do just that in experiments that were carried out at the NEIDL in Boston.
“I was skeptical at the beginning because it seemed too good to be true,” says NEIDL microbiologist Anna Honko, one of the co-first authors on the study. “But when I saw the first set of results in the lab, I was just astonished.”
The technology consists of very small, nanosized drops of polymers–essentially, soft biofriendly plastics–covered in fragments of living lung cell and immune cell membranes.
“It looks like a nanoparticle coated in pieces of cell membrane,” Honko says. “The small polymer [droplet] mimics a cell having a membrane around it.”
The SARS-CoV-2 virus seeks out unique signatures of lung cell membranes and latches onto them. When that happens inside the human body, the coronavirus infection takes hold, with the SARS-CoV-2 viruses hijacking lung cells to replicate their own genetic material. But in experiments at the NEIDL, BU researchers observed that polymer droplets laden with pieces of lung cell membrane did a better job of attracting the SARS-CoV-2 virus than living lung cells. [emphasis mine]
By fusing with the SARS-CoV-2 virus better than living cells can, the nanotechnology appears to be an effective countermeasure to coronavirus infection, preventing SARS-CoV-2 from attacking cells.
“Our guess is that it acts like a decoy, it competes with cells for the virus,” says NEIDL microbiologist Anthony Griffiths, co-corresponding author on the study. “They are little bits of plastic, just containing the outer pieces of cells with none of the internal cellular machinery contained inside living cells. Conceptually, it’s such a simple idea. It mops up the virus like a sponge.”
That attribute is why the UC San Diego and BU research team call the technology “nanosponges.” Once SARS-CoV-2 binds with the cell fragments inside a nanosponge droplet–each one a thousand times smaller than the width of a human hair–the coronavirus dies. Although the initial results are based on experiments conducted in cell culture dishes, the researchers believe that inside a human body, the biodegradable nanosponges and the SARS-CoV-2 virus trapped inside them could then be disposed of by the body’s immune system. The immune system routinely breaks down and gets rid of dead cell fragments caused by infection or normal cell life cycles.
There is also another important effect that the nanosponges have in the context of coronavirus infection. Honko says nanosponges containing fragments of immune cells can soak up cellular signals that increase inflammation [emphases mine]. Acute respiratory distress, caused by an inflammatory cascade inside the lungs, is the most deadly aspect of the coronavirus infection, sending patients into the intensive care unit for oxygen or ventilator support to help them breathe.
But the nanosponges, which can attract the inflammatory molecules that send the immune system into dangerous overdrive, can help tamp down that response, Honko says. By using both kinds of nanosponges, some containing lung cell fragments and some containing pieces of immune cells, she says it’s possible to “attack the coronavirus and the [body’s] response” responsible for disease and eventual lung failure.
At the NEIDL, Honko and Griffiths are now planning additional experiments to see how well the nanosponges can prevent coronavirus infection in animal models of the disease. They plan to work closely with the team of engineers at UC San Diego, who first developed the nanosponges more than a decade ago, to tailor the technology for eventual safe and effective use in humans.
“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets,” said Liangfang Zhang, a UC San Diego nanoengineer and leader of the California-based team, according to a UC San Diego press release. “Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys.”
When the novel coronavirus first appeared, the idea of using the nanosponges to combat the infection came to Zhang almost immediately. He reached out to the NEIDL for help. Looking ahead, the BU and UC San Diego collaborators believe the nanosponges can easily be converted into a noninvasive treatment.
“We should be able to drop it right into the nose,” Griffiths says. “In humans, it could be something like a nasal spray.”
Honko agrees: “That would be an easy and safe administration method that should target the appropriate [respiratory] tissues. And if you wanted to treat patients that are already intubated, you could deliver it straight into the lung.”
Griffiths and Honko are especially intrigued by the nanosponges as a new platform for treating all types of viral infections. “The broad spectrum aspect of this is exceptionally appealing,” Griffiths says. The researchers say the nanosponge could be easily adapted to house other types of cell membranes preferred by other viruses, creating many new opportunities to use the technology against other tough-to-treat infections like the flu and even deadly hemorrhagic fevers caused by Ebola, Marburg, or Lassa viruses.
“I’m interested in seeing how far we can push this technology,” Honko says.
The University of California as San Diego has released a video illustrating the nanosponges work,
Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce.
The first data describing this new direction for fighting COVID-19 were published on June 17 in the journal Nano Letters. The “nanosponges” were developed by engineers at the University of California San Diego and tested by researchers at Boston University.
The UC San Diego researchers call their nano-scale particles “nanosponges” because they soak up harmful pathogens and toxins.
In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its “viral infectivity” in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.
Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades.
“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering.
His lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since [emphasis mine]. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang “almost immediately,” he said.
In addition to the encouraging data on neutralizing the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of COVID-19 and are driven by immune response to the infection.
Making and testing COVID-19 nanosponges
Each COVID-19 nanosponge–a thousand times smaller than the width of a human hair–consists of a polymer core coated in cell membranes extracted from either lung epithelial type II cells or macrophage cells. The membranes cover the sponges with all the same protein receptors as the cells they impersonate–and this inherently includes whatever receptors SARS-CoV-2 uses to enter cells in the body.
The researchers prepared several different concentrations of nanosponges in solution to test against the novel coronavirus. To test the ability of the nanosponges to block SARS-CoV-2 infectivity, the UC San Diego researchers turned to a team at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) to perform independent tests. In this BSL-4 lab–the highest biosafety level for a research facility–the researchers, led by Anthony Griffiths, associate professor of microbiology at Boston University School of Medicine, tested the ability of various concentrations of each nanosponge type to reduce the infectivity of live SARS-CoV-2 virus–the same strains that are being tested in other COVID-19 therapeutic and vaccine research.
At a concentration of 5 milligrams per milliliter, the lung cell membrane-cloaked sponges inhibited 93% of the viral infectivity of SARS-CoV-2. The macrophage-cloaked sponges inhibited 88% of the viral infectivity of SARS-CoV-2. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.
“From the perspective of an immunologist and virologist, the nanosponge platform was immediately appealing as a potential antiviral because of its ability to work against viruses of any kind. This means that as opposed to a drug or antibody that might very specifically block SARS-CoV-2 infection or replication, these cell membrane nanosponges might function in a more holistic manner in treating a broad spectrum of viral infectious diseases. I was optimistically skeptical initially that it would work, and then thrilled once I saw the results and it sunk in what this could mean for therapeutic development as a whole,” said Anna Honko, a co-first author on the paper and a Research Associate Professor, Microbiology at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL).
In the next few months, the UC San Diego researchers and collaborators will evaluate the nanosponges’ efficacy in animal models. The UC San Diego team has already shown short-term safety in the respiratory tracts and lungs of mice. If and when these COVID-19 nanosponges will be tested in humans depends on a variety of factors, but the researchers are moving as fast as possible.
“Another interesting aspect of our approach is that even as SARS-CoV-2 mutates, as long as the virus can still invade the cells we are mimicking, our nanosponge approach should still work. I’m not sure this can be said for some of the vaccines and therapeutics that are currently being developed,” said Zhang.
The researchers also expect these nanosponges would work against any new coronavirus or even other respiratory viruses, including whatever virus might trigger the next respiratory pandemic.
Mimicking lung epithelial cells and immune cells
Since the novel coronavirus often infects lung epithelial cells as the first step in COVID-19 infection, Zhang and his colleagues reasoned that it would make sense to cloak a nanoparticle in fragments of the outer membranes of lung epithelial cells to see if the virus could be tricked into latching on it instead of a lung cell.
Macrophages, which are white blood cells that play a major role in inflammation, also are very active in the lung during the course of a COVID-19 illness, so Zhang and colleagues created a second sponge cloaked in macrophage membrane.
The research team plans to study whether the macrophage sponges also have the ability to quiet cytokine storms in COVID-19 patients.
“We will see if the macrophage nanosponges can neutralize the excessive amount of these cytokines as well as neutralize the virus,” said Zhang.
Using macrophage cell fragments as cloaks builds on years of work to develop therapies for sepsis using macrophage nanosponges.
In a paper published in 2017 in Proceedings of the National Academy of Sciences, Zhang and a team of researchers at UC San Diego showed that macrophage nanosponges can safely neutralize both endotoxins and pro-inflammatory cytokines in the bloodstream of mice. A San Diego biotechnology company co-founded by Zhang called Cellics Therapeutics is working to translate this macrophage nanosponge work into the clinic.
A potential COVID-19 therapeutic The COVID-19 nanosponge platform has significant testing ahead of it before scientists know whether it would be a safe and effective therapy against the virus in humans, Zhang cautioned [emphasis mine]. But if the sponges reach the clinical trial stage, there are multiple potential ways of delivering the therapy that include direct delivery into the lung for intubated patients, via an inhaler like for asthmatic patients, or intravenously, especially to treat the complication of cytokine storm.
A therapeutic dose of nanosponges might flood the lung with a trillion or more tiny nanosponges that could draw the virus away from healthy cells. Once the virus binds with a sponge, “it loses its viability and is not infective anymore, and will be taken up by our own immune cells and digested,” said Zhang.
“I see potential for a preventive treatment, for a therapeutic that could be given early because once the nanosponges get in the lung, they can stay in the lung for some time,” Zhang said. “If a virus comes, it could be blocked if there are nanosponges waiting for it.”
Growing momentum for nanosponges
Zhang’s lab at UC San Diego created the first membrane-cloaked nanoparticles over a decade ago. The first of these nanosponges were cloaked with fragments of red blood cell membranes. These nanosponges are being developed to treat bacterial pneumonia and have undergone all stages of pre-clinical testing by Cellics Therapeutics, the San Diego startup cofounded by Zhang. The company is currently in the process of submitting the investigational new drug (IND) application to the FDA for their lead candidate: red blood cell nanosponges for the treatment of methicillin-resistant staphylococcus aureus (MRSA) pneumonia. The company estimates the first patients in a clinical trial will be dosed next year.
The UC San Diego researchers have also shown that nanosponges can deliver drugs to a wound site; sop up bacterial toxins that trigger sepsis; and intercept HIV before it can infect human T cells.
The basic construction for each of these nanosponges is the same: a biodegradable, FDA-approved polymer core is coated in a specific type of cell membrane, so that it might be disguised as a red blood cell, or an immune T cell or a platelet cell. The cloaking keeps the immune system from spotting and attacking the particles as dangerous invaders.
“I think of the cell membrane fragments as the active ingredients. This is a different way of looking at drug development,” said Zhang. “For COVID-19, I hope other teams come up with safe and effective therapies and vaccines as soon as possible. At the same time, we are working and planning as if the world is counting on us.”
I wish the researchers good luck. For the curious, here’s a link to and a citation for the paper,
A molecule that protects plants from overexposure to harmful sunlight thanks to its flamenco-style twist could form the basis for a new longer-lasting sunscreen, chemists at the University of Warwick have found, in collaboration with colleagues in France and Spain. Research on the green molecule by the scientists has revealed that it absorbs ultraviolet light and then disperses it in a ‘flamenco-style’ dance, making it ideal for use as a UV filter in sunscreens.
The team of scientists report today, Friday 18th October 2019, in the journal Nature Communications that, as well as being plant-inspired, this molecule is also among a small number of suitable substances that are effective in absorbing light in the Ultraviolet A (UVA) region of wavelengths. It opens up the possibility of developing a naturally-derived and eco-friendly sunscreen that protects against the full range of harmful wavelengths of light from the sun.
The UV filters in a sunscreen are the ingredients that predominantly provide the protection from the sun’s rays. In addition to UV filters, sunscreens will typically also include:
Emollients, used for moisturising and lubricating the skin Thickening agents Emulsifiers to bind all the ingredients Water Other components that improve aesthetics, water resistance, etc.
The researchers tested a molecule called diethyl sinapate, a close mimic to a molecule that is commonly found in the leaves of plants, which is responsible for protecting them from overexposure to UV light while they absorb visible light for photosynthesis.
They first exposed the molecule to a number of different solvents to determine whether that had any impact on its (principally) light absorbing behaviour. They then deposited a sample of the molecule on an industry standard human skin mimic (VITRO-CORNEUM®) where it was irradiated with different wavelengths of UV light. They used the state-of-the-art laser facilities within the Warwick Centre for Ultrafast Spectroscopy to take images of the molecule at extremely high speeds, to observe what happens to the light’s energy when it’s absorbed in the molecule in the very early stages (millionths of millionths of a second). Other techniques were also used to establish longer term (many hours) properties of diethyl sinapate, such as endocrine disruption activity and antioxidant potential.
Professor Vasilios Stavros from the University of Warwick, Department of Chemistry, who was part of the research team, explains: “A really good sunscreen absorbs light and converts it to harmless heat. A bad sunscreen is one that absorbs light and then, for example, breaks down potentially inducing other chemistry that you don’t want. Diethyl sinapate generates lots of heat, and that’s really crucial.”
When irradiated the molecule absorbs light and goes into an excited state but that energy then has to be disposed of somehow. The team of researchers observed that it does a kind of molecular ‘dance’ a mere 10 picoseconds (ten millionths of a millionth of a second) long: a twist in a similar fashion to the filigranas and floreos hand movements of flamenco dancers. That causes it to come back to its original ground state and convert that energy into vibrational energy, or heat.
It is this ‘flamenco dance’ that gives the molecule its long-lasting qualities. When the scientists bombarded the molecule with UVA light they found that it degraded only 3% over two hours, compared to the industry requirement of 30%.
Dr Michael Horbury, who was a Postgraduate Research Fellow at The University Warwick when he undertook this research (and now at the University of Leeds) adds: “We have shown that by studying the molecular dance on such a short time-scale, the information that you gain can have tremendous repercussions on how you design future sunscreens. Emily Holt, a PhD student in the Department of Chemistry at the University of Warwick who was part of the research team, said: “The next step would be to test it on human skin, then to mix it with other ingredients that you find in a sunscreen to see how those affect its characteristics.”
Professor Florent Allais and Dr Louis Mouterde, URD Agro-Biotechnologies Industrielles at AgroParisTech (Pomacle, France) commented: “What we have developed together is a molecule based upon a UV photoprotective molecule found in the surface of leaves on a plant and refunctionalised it using greener synthetic procedures. Indeed, this molecule has excellent long-term properties while exhibiting low endocrine disruption and valuable antioxidant properties.”
Professor Laurent Blasco, Global Technical Manager (Skin Essentials) at Lubrizol and Honorary Professor at the University of Warwick commented: “In sunscreen formulations at the moment there is a lack of broad-spectrum protection from a single UV filter. Our collaboration has gone some way towards developing a next generation broad-spectrum UV filter inspired by nature. Our collaboration has also highlighted the importance of academia and industry working together towards a common goal.”
Professor Vasilios Stavros added, “Amidst escalating concerns about their impact on human toxicity (e.g. endocrine disruption) and ecotoxicity (e.g. coral bleaching), developing new UV filters is essential. We have demonstrated that a highly attractive avenue is ‘nature-inspired’ UV filters, which provide a front-line defence against skin cancer and premature skin aging.”
Here’s a link to and a citation for the paper,
Towards symmetry driven and nature inspired UV filter design by Michael D. Horbury, Emily L. Holt, Louis M. M. Mouterde, Patrick Balaguer, Juan Cebrián, Laurent Blasco, Florent Allais & Vasilios G. Stavros. Nature Communications volume 10, Article number: 4748 (2019) DOI: https://doi.org/10.1038/s41467-019-12719-z
This paper is open access.
Why the high hopes?
Briefly (the long story stretches over 10 years), the most recommended sunscreens today (2020) are ‘mineral-based’. This is painfully amusing because civil society groups (activists) such as Friends of the Earth (in particular the Australia chapter under Georgia Miller’s leadership) and Canada’s own ETC Group had campaigned against these same sunscreen when they were billed as being based on metal oxide nanoparticles such zinc oxide and/or titanium oxide. The ETC Group under Pat Roy Mooney’s leadership didn’t press the campaign after an initial push. As for Australia and Friend of the Earth, their anti-metallic oxide nanoparticle sunscreen campaign didn’t work out well as I noted in a February 9, 2012 posting and with a follow-up in an October 31, 2012 posting.
The only civil society group to give approval (very reluctantly) was the Environmental Working Group (EWG) as I noted in a July 9, 2009 posting. They had concerns about the fact that these ingredients are metallic but after a thorough of then available research, EWG gave the sunscreens a passing grade and noted, in their report, that they had more concerns about the use of oxybenzone in sunscreens. That latter concern has since been flagged by others (e.g., the state of Hawai’i) as noted in my July 6, 2018 posting.
So, rebranding metallic oxides as minerals has allowed the various civil society groups to support the very same sunscreens many of them were advocating against.
In the meantime, scientists continue work on developing plant-based sunscreens as an improvement to the ‘mineral-based’ sunscreens used now.
The last time I wrote about memcapacitors (June 30, 2014 posting: Memristors, memcapacitors, and meminductors for faster computers), the ideas were largely theoretical; I believe this work is the first research I’ve seen on the topic. From an October 17, 2019 news item on ScienceDaily,
Researchers at the Department of Energy’s Oak Ridge National Laboratory ]ORNL], the University of Tennessee and Texas A&M University demonstrated bio-inspired devices that accelerate routes to neuromorphic, or brain-like, computing.
Results published in Nature Communications report the first example of a lipid-based “memcapacitor,” a charge storage component with memory that processes information much like synapses do in the brain. Their discovery could support the emergence of computing networks modeled on biology for a sensory approach to machine learning.
“Our goal is to develop materials and computing elements that work like biological synapses and neurons—with vast interconnectivity and flexibility—to enable autonomous systems that operate differently than current computing devices and offer new functionality and learning capabilities,” said Joseph Najem, a recent postdoctoral researcher at ORNL’s Center for Nanophase Materials Sciences, a DOE Office of Science User Facility, and current assistant professor of mechanical engineering at Penn State.
The novel approach uses soft materials to mimic biomembranes and simulate the way nerve cells communicate with one another.
The team designed an artificial cell membrane, formed at the interface of two lipid-coated water droplets in oil, to explore the material’s dynamic, electrophysiological properties. At applied voltages, charges build up on both sides of the membrane as stored energy, analogous to the way capacitors work in traditional electric circuits.
But unlike regular capacitors, the memcapacitor can “remember” a previously applied voltage and—literally—shape how information is processed. The synthetic membranes change surface area and thickness depending on electrical activity. These shapeshifting membranes could be tuned as adaptive filters for specific biophysical and biochemical signals.
“The novel functionality opens avenues for nondigital signal processing and machine learning modeled on nature,” said ORNL’s Pat Collier, a CNMS staff research scientist.
A distinct feature of all digital computers is the separation of processing and memory. Information is transferred back and forth from the hard drive and the central processor, creating an inherent bottleneck in the architecture no matter how small or fast the hardware can be.
Neuromorphic computing, modeled on the nervous system, employs architectures that are fundamentally different in that memory and signal processing are co-located in memory elements—memristors, memcapacitors and meminductors.
These “memelements” make up the synaptic hardware of systems that mimic natural information processing, learning and memory.
Systems designed with memelements offer advantages in scalability and low power consumption, but the real goal is to carve out an alternative path to artificial intelligence, said Collier.
Tapping into biology could enable new computing possibilities, especially in the area of “edge computing,” such as wearable and embedded technologies that are not connected to a cloud but instead make on-the-fly decisions based on sensory input and past experience.
Biological sensing has evolved over billions of years into a highly sensitive system with receptors in cell membranes that are able to pick out a single molecule of a specific odor or taste. “This is not something we can match digitally,” Collier said.
Digital computation is built around digital information, the binary language of ones and zeros coursing through electronic circuits. It can emulate the human brain, but its solid-state components do not compute sensory data the way a brain does.
“The brain computes sensory information pushed through synapses in a neural network that is reconfigurable and shaped by learning,” said Collier. “Incorporating biology—using biomembranes that sense bioelectrochemical information—is key to developing the functionality of neuromorphic computing.”
While numerous solid-state versions of memelements have been demonstrated, the team’s biomimetic elements represent new opportunities for potential “spiking” neural networks that can compute natural data in natural ways.
Spiking neural networks are intended to simulate the way neurons spike with electrical potential and, if the signal is strong enough, pass it on to their neighbors through synapses, carving out learning pathways that are pruned over time for efficiency.
A bio-inspired version with analog data processing is a distant aim. Current early-stage research focuses on developing the components of bio-circuitry.
“We started with the basics, a memristor that can weigh information via conductance to determine if a spike is strong enough to be broadcast through a network of synapses connecting neurons,” said Collier. “Our memcapacitor goes further in that it can actually store energy as an electric charge in the membrane, enabling the complex ‘integrate and fire’ activity of neurons needed to achieve dense networks capable of brain-like computation.”
The team’s next steps are to explore new biomaterials and study simple networks to achieve more complex brain-like functionalities with memelements.
Here’s a link to and a citation for the paper,
Dynamical nonlinear memory capacitance in biomimetic membranes by Joseph S. Najem, Md Sakib Hasan, R. Stanley Williams, Ryan J. Weiss, Garrett S. Rose, Graham J. Taylor, Stephen A. Sarles & C. Patrick Collier. Nature Communications volume 10, Article number: 3239 (2019) DOI: DOIhttps://doi.org/10.1038/s41467-019-11223-8 Published July 19, 2019
This paper is open access.
One final comment, you might recognize one of the authors (R. Stanley Williams) who in 2008 helped launch ‘memristor’ research.
Despite all the promise that nanocellulose offers, scientists don’t seem to have found significant applications for the material . In the software industry, they used to call it ‘a killer app’, i.e., an application everyone would start using (e.g. Facebook or Google) thereby making much money for its developer(s)..
This July 31, 2019 news item on phys.org describes research that may help scientists develop a nanocellulose ‘killer app’,
High-performance biomass-based nanocomposites are emerging as promising materials for future structural and functional applications due to their environmentally friendly, renewable and sustainable characteristics. Bio-sourced nanocelluloses [sic] (a kind of nanofibers [sic]) obtained from plants and bacterial fermentation are the most abundant raw materials on earth. They have attracted tremendous attention recently due to their attractive inherent merits including biodegradability, low density, thermal stability, global availability from renewable resources, as well as impressive mechanical properties. These features make them appropriate building blocks for spinning the next generation of advanced macrofibers for practical applications.
In past decades, various strategies have been pursued to gain cellulose-based macrofibers with improved strength and stiffness. However, nearly all of them have been achieved at the expense of elongation and toughness, because strength and toughness are always mutually exclusive for man-made structural materials. Therefore, this dilemma is quite common for previously reported cellulose-based macrofibers, which greatly limited their practical applications.
In a new article published in the National Science Review, Recently, a bionics research team led by Prof. Yu Shuhong from the University of Science and Technology of China (USTC) sought an inspiration to solve this problem from biological structures. …
… They found that the widespread biosynthesized fibers, such as some plant fibers, spider silk and animal hairs, all have some similar features. They are both strong and tough, and have hierarchical helical structures across multiple length scales with stiff and strong nanoscale fibrous building blocks embedded in soft and energy dissipating matrices.
Inspired by these structural features in biosynthesized fibers, they presented a design strategy to make nanocellulose-based macrofibers with similar structural features. They used bacterial cellulose nanofibers as the strong and stiff building blocks, sodium alginate as the soft matrix. By combining a facile wet-spinning process with a subsequent multiple wet-twisting procedure, they successfully obtained biomimetic hierarchical helical nanocomposite macrofibers, and realized impressive improvement of their tensile strength, elongation and toughness simultaneously as expected.
This achievement certifies the validity of their bioinspired design and provides a potential route for further creating many other strong and tough nanocomposite fiber materials for diverse applications.