The discovery, described Apr. 3 in Current Biology, adds to the scientific understanding of how vision — far from being a mere absorption of incoming signals from the retina — is controlled and directed by cognitive processes.

“These eye movements are so tiny that we’re not even conscious of them, and yet our brains somehow can use the knowledge of the visual task to control them,” says study lead author Dr. Yen-Chu Lin, who carried out the work as a Fred Plum Fellow in Systems Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.

Dr. Lin works in the laboratory of study senior author Dr. Jonathan Victor, the Fred Plum Professor of Neurology at Weill Cornell Medicine.

The study involved a close collaboration with the laboratory of Dr. Michele Rucci, professor of brain and cognitive sciences and neuroscience at the University of Rochester.

Neuroscientists have known for decades that information stored in memory can strongly shape the processing of sensory inputs, including the streams of visual data coming from the eyes. In other words, what we see is influenced by what we expect to see or the requirements of the task at hand.

Most studies of cognitive control over eye movement have covered more obvious movements, such as the “saccade” movements in which the eyes dart across large parts of the visual field. In the new study, Drs. Lin and Victor and their colleagues examined ocular drift, tiny jitters of the eye that occur even when gaze seems fixed. Ocular drifts are subtle motions that shift a visual target on the retina by distances on the order of a fraction of a millimeter or so — across just a few dozen photoreceptors (cones). They are thought to improve detection of small, stationary details in a visual scene by scanning across them, effectively converting spatial details into trains of visual signals in time.

Prior studies had suggested that ocular drift and other small-scale “fixational eye movements” are under cognitive control only in a broad sense — for example, slowing when scanning across more finely detailed scenes. In the new study, the researchers found evidence for a more precise type of control.

Using sensitive equipment in Dr. Rucci’s laboratory, the researchers recorded ocular drifts in six volunteers who were asked to identify which of a pair of letters (H vs. N, or E vs. F) was being shown to them on a background of random visual noise. Based on computational modeling, the scientists expected that optimal eye movements for discriminating between letters would cross the key elements distinguishing the letters at right angles. Thus, they hypothesized that a more precise cognitive control, if it existed, would tend to direct ocular drift in both vertical and oblique (lower left to upper right) directions for the H vs. N discrimination, compared to more strictly vertical movements for the E vs. F discrimination.

They found that the subjects’ eye movements did indeed tend to follow these patterns — even in the 20 percent of trials in which the subjects, though expecting to see a letter, were shown only noise. The latter result showed that the cognitive control of ocular drift could be driven solely by specific prior knowledge of the visual task, independently of any incoming visual information.

“These results underscore the interrelationship between the sensory and the motor parts of vision — one really can’t view them separately,” said Dr. Victor, who is also a professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell.

He noted that the direction of fine eye movements is thought to come from neurons in the brainstem, whereas the task knowledge presumably resides in the upper brain: the cortex — implying some kind of non-conscious connection between them.

“The subjects are aware of the tasks they have to do, yet they don’t know that their eyes are executing these tiny movements, even when you tell them,” Dr. Victor said.

Studies of this pathway, he added, could lead to better insights not only into the neuroscience of vision, but possibly also visual disorders — which traditionally have been seen as disorders of the retina or sensory processing within the brain.

“What our findings suggest is that visual disorders may sometimes have a motor component too, since optimal vision depends on the brain’s ability to execute these very tiny movements,” Dr. Victor said.

Many robotic hands pack all their powerful sensors into the fingertips, so an object must be in full contact with those fingertips to be identified, which can take multiple grasps. Other designs use lower-resolution sensors spread along the entire finger, but these don’t capture as much detail, so multiple regrasps are often required.

Instead, the MIT team built a robotic finger with a rigid skeleton encased in a soft outer layer that has multiple high-resolution sensors incorporated under its transparent “skin.” The sensors, which use a camera and LEDs to gather visual information about an object’s shape, provide continuous sensing along the finger’s entire length. Each finger captures rich data on many parts of an object simultaneously.

Using this design, the researchers built a three-fingered robotic hand that could identify objects after only one grasp, with about 85 percent accuracy. The rigid skeleton makes the fingers strong enough to pick up a heavy item, such as a drill, while the soft skin enables them to securely grasp a pliable item, like an empty plastic water bottle, without crushing it.

These soft-rigid fingers could be especially useful in an at-home-care robot designed to interact with an elderly individual. The robot could lift a heavy item off a shelf with the same hand it uses to help the individual take a bath.

“Having both soft and rigid elements is very important in any hand, but so is being able to perform great sensing over a really large area, especially if we want to consider doing very complicated manipulation tasks like what our own hands can do. Our goal with this work was to combine all the things that make our human hands so good into a robotic finger that can do tasks other robotic fingers can’t currently do,” says mechanical engineering graduate student Sandra Liu, co-lead author of a research paper on the robotic finger.

Liu wrote the paper with co-lead author and mechanical engineering undergraduate student Leonardo Zamora Yañez and her advisor, Edward Adelson, the John and Dorothy Wilson Professor of Vision Science in the Department of Brain and Cognitive Sciences and a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL). The research will be presented at the RoboSoft Conference.

A human-inspired finger

The robotic finger is comprised of a rigid, 3D-printed endoskeleton that is placed in a mold and encased in a transparent silicone “skin.” Making the finger in a mold removes the need for fasteners or adhesives to hold the silicone in place.

The researchers designed the mold with a curved shape so the robotic fingers are slightly curved when at rest, just like human fingers.

“Silicone will wrinkle when it bends, so we thought that if we have the finger molded in this curved position, when you curve it more to grasp an object, you won’t induce as many wrinkles. Wrinkles are good in some ways — they can help the finger slide along surfaces very smoothly and easily — but we didn’t want wrinkles that we couldn’t control,” Liu says.

The endoskeleton of each finger contains a pair of detailed touch sensors, known as GelSight sensors, embedded into the top and middle sections, underneath the transparent skin. The sensors are placed so the range of the cameras overlaps slightly, giving the finger continuous sensing along its entire length.

The GelSight sensor, based on technology pioneered in the Adelson group, is composed of a camera and three colored LEDs. When the finger grasps an object, the camera captures images as the colored LEDs illuminate the skin from the inside.

Using the illuminated contours that appear in the soft skin, an algorithm performs backward calculations to map the contours on the grasped object’s surface. The researchers trained a machine-learning model to identify objects using raw camera image data.

As they fine-tuned the finger fabrication process, the researchers ran into several obstacles.

First, silicone has a tendency to peel off surfaces over time. Liu and her collaborators found they could limit this peeling by adding small curves along the hinges between the joints in the endoskeleton.

When the finger bends, the bending of the silicone is distributed along the tiny curves, which reduces stress and prevents peeling. They also added creases to the joints so the silicone is not squashed as much when the finger bends.

While troubleshooting their design, the researchers realized wrinkles in the silicone prevent the skin from ripping.

“The usefulness of the wrinkles was an accidental discovery on our part. When we synthesized them on the surface, we found that they actually made the finger more durable than we expected,” she says.

Getting a good grasp

Once they had perfected the design, the researchers built a robotic hand using two fingers arranged in a Y pattern with a third finger as an opposing thumb. The hand captures six images when it grasps an object (two from each finger) and sends those images to a machine-learning algorithm which uses them as inputs to identify the object.

Because the hand has tactile sensing covering all of its fingers, it can gather rich tactile data from a single grasp.

“Although we have a lot of sensing in the fingers, maybe adding a palm with sensing would help it make tactile distinctions even better,” Liu says.

In the future, the researchers also want to improve the hardware to reduce the amount of wear and tear in the silicone over time and add more actuation to the thumb so it can perform a wider variety of tasks.

This work was supported, in part, by the Toyota Research Institute, the Office of Naval Research, and the SINTEF BIFROST project.

Zachariah Reagh, an assistant professor of psychological and brain sciences in Arts & Sciences at Washington University in St. Louis, and co-author Charan Ranganath of the University of California, Davis, used functional MRI scanners to monitor the brains of subjects watching short videos of scenes that could have come from real life. These included men and women working on laptops in a cafe or shopping in a grocery store.

“They were very ordinary scenes,” Reagh said. “No car chases or anything.”

The research subjects then immediately described the scenes with as much detail as they could muster. The mundane snippets led to intriguing findings, including that different parts of the brain worked together to understand and remember a situation.

Networks in the front part of the temporal lobe, a region of the brain long known to play an important role in memory, focused on the subject regardless of their surroundings. But the posterior medial network, which involves the parietal lobe toward the back of the brain, paid more attention to the environment. Those networks then sent information to the hippocampus, Reagh explained, which combined the signals to create a cohesive scene.

Researchers had previously used very simple objects and scenarios — such as a picture of an apple on a beach — to study the different building blocks of memories, Reagh said. But life isn’t so simple, he said. “I wondered if anyone had done these types of studies with dynamic real-word situations and, shockingly, the answer was no.”

The new study suggests that the brain makes mental sketches of people that can be transposed from one location to another, much like an animator can copy and paste a character into different scenes. “It may not seem intuitive that your brain can create a sketch of a family member that it moves from place to place, but it’s very efficient,” he said.

Some subjects could recall the scenes in the café and grocery store more completely and accurately than others. Reagh and Ranganath found that those with the clearest memories used the same neural patterns when recalling scenes that they used while watching the clips. “The more you can bring those patterns back online while describing an event, the better your overall memory,” he said.

At this time, Reagh said, it’s unclear why some people seem more adept than others at reproducing the thought patterns needed to access memory. But it’s clear that many things can get in the way. “A lot can go wrong when you try to retrieve a memory,” he said.

Even memories that seem crisp and vivid may not actually reflect reality. “I tell my students that your memory is not a video camera. It doesn’t give you a perfect representation of what happened. Your brain is telling you a story,” he said.

Reagh is one of the Washington University faculty members involved in the research cluster “The Storytelling Lab: Bridging Science, Technology, and Creativity,” part of the Incubator for Transdisciplinary Futures. Led by Jeff Zacks, chair of the Department of Psychological & Brain Sciences, with Ian Bogost and Colin Burnett, the Storytelling Lab explores the psychology and neurology of narratives.

In future, Reagh plans to study the brain activity and memory of people watching more complicated stories.

“The Storytelling Lab fits perfectly with the scientific questions that I find most exciting,” Reagh said. “I want to understand how the brain creates and remembers narratives.”

Now Northwestern University researchers have developed a new technology that makes it easier to eavesdrop on our body’s inner conversations.

While the body’s chemical signals are incredibly faint — making them difficult to detect and analyze — the researchers have developed a new method that boosts signals by more than 1,000 times. Transistors, the building block of electronics, can boost weak signals to provide an amplified output. The new approach makes signals easier to detect without complex and bulky electronics.

By enabling amplification of weak biochemical signals, the new approach brings modern medicine one step closer to real-time, on-site diagnostics and disease monitoring.

The research was published Saturday (March 24) in the journal Nature Communications.

“If we could reliably measure biochemical signals in the body, we could incorporate those sensors into wearable technologies or implants that have a small footprint, less burden and don’t require expensive electronics,” said Northwestern’s Jonathan Rivnay, the study’s senior author. “But extracting high-quality signals has remained a challenge. With limited power and space inside the body, you need to find ways to amplify those signals.”

Rivnay is a professor of biomedical engineering at Northwestern’s McCormick School of Engineering. Xudong Ji, a post-doctoral researcher in Rivnay’s laboratory, is the paper’s first author.

While they communicate vital information packed with potential to guide diagnoses and treatment, many chemical sensors produce weak signals. In fact, health care professionals often cannot decipher these signals without removing a sample (blood, sweat, saliva) and running it through high-tech laboratory equipment. Usually, this equipment is expensive and perhaps even located off-site. And results can take an excruciatingly long time to return.

Rivnay’s team, however, aims to sense and amplify these hidden signals without ever leaving the body.

Other researchers have explored electrochemical sensors for biosensing using aptamers, which are single strands of DNA engineered to bind to specific targets. After successfully binding to a target of interest, aptamers act like an electronic switch, folding into a new structure that triggers an electrochemical signal. But with aptamers alone, the signals are often weak and highly susceptible to noise and distortion if not tested under ideal and well-controlled conditions.

To bypass this issue, Rivnay’s team equipped an amplifying component onto a traditional electrode-based sensor and developed an electrochemical transistor-based sensor with new architecture that can sense and amplify the weak biochemical signal. In this new device, the electrode is used to sense a signal, but the nearby transistor is dedicated to amplifying the signal. The researchers also incorporated a built-in, thin-film reference electrode to make the amplified signals more stable and reliable.

“We combine the power of the transistor for local amplification with the referencing you get from well-established electrochemical methods,” Ji said. “It’s the best of both worlds because we’re able to stably measure the aptamer binding and amplify it on site.”

To validate the new technology, Rivnay’s team turned to a common cytokine, a type of signaling protein, that regulates immune response and is implicated in tissue repair and regeneration. By measuring the concentration of certain cytokines near a wound, researchers can assess how quickly a wound is healing, if there is a new infection or whether or not other medical interventions are required.

In a series of experiments, Rivnay and his team were able to amplify the cytokines’ signal by three-to-four orders of magnitude compared with traditional electrode-based aptamer sensing methods. Although the technology performed well in experiments to sense cytokine signaling, Rivnay says it should be able to amplify signals from any molecule or chemical, including antibodies, hormones or drugs, where the detection scheme uses electrochemical reporters.

“This approach is broadly applicable and doesn’t have a specific use case,” Rivnay said. “The big vision is to implement our concept into implantable biosensors or wearable devices that can both sense a problem and then respond it.”

The study, “Organic electrochemical transistors as on-site signal amplifier for electrochemical aptamer-based sensing,” was supported by the Defense Advanced Research Projects Agency (grant number D20AC00002).

The approach uses an innovative copper-containing polymeric filter and essentially converts CO₂ into sodium bicarbonate (aka baking soda) that can be released harmlessly into the ocean. This new hybrid material, or filter, is called DeCarbonHIX (i.e., decarbonization through hybrid ion exchange material), and is described in a paper recently published in the journal Science Advances.

The research, which demonstrated a 300 percent increase in the amount of carbon captured compared with existing direct air capture methods, has garnered international attention from media outlets like the BBC, CNN, Fast Company, and The Daily Beast, and professional organizations like the American Chemical Society. SenGupta himself has been fielding interest in the technology from companies based in Brazil, Ireland, and the Middle East.

“The climate crisis is an international problem,” says SenGupta, who is a professor of chemical and biomolecular engineering and civil and environmental engineering in Lehigh’s P.C. Rossin College of Engineering and Applied Science. “And I believe we have a responsibility to build direct air capture technology in a way that it can be implemented by people and countries around the world. Anyone who can operate a cell phone should be able to operate this process. This is not technology for making money. It’s for saving the world.”

The work is yet another extension of SenGupta’s personal and professional commitment to developing technologies that benefit humanity, and in particular, marginalized communities around the world. His research on water science and technology has included drinking water treatment methodologies, desalination, municipal wastewater reuse, and resource recovery. He invented the first reusable, arsenic-selective hybrid anion exchanger nanomaterial (HAIX-Nano), and as a result, more than two million people around the world now drink arsenic-safe water. Two of his patents have been recognized as “Patents for Humanity” by the US patent and Trademark Office.

His invention of DeCarbonHIX was the outcome of an ongoing CO₂-driven wastewater desalination project funded by the Bureau of Reclamation under the jurisdiction of the U.S. Department of the Interior. SenGupta and his students were on the lookout for a reliable supply of CO₂ even in remote places. That quest led the way to the field of direct air capture, or DAC, and the creation of DeCarbonHIX. This subject was the dissertation topic for environmental engineering student Hao Chen ’23 PhD, who successfully defended his PhD in March and will receive his doctorate in May.

Capturing carbon at lower concentrations

The most abundant of the greenhouse gasses contributing to global warming is carbon dioxide. In 2021, global emissions of CO₂ rose by 6 percent from the previous year — to 36.3 gigatons, according to the International Energy Agency. Just one gigaton (equal to 1 billion tons) is the equivalent of the mass of all land mammals on earth.

Emissions from greenhouse gasses have increased global temperatures by approximately 1.1 degrees Celsius above pre-industrial levels, according to the Intergovernmental Panel on Climate Change. In its 2021 working group report, the IPCC estimates the average yearly temperature over the next 20 years is expected to rise by at least 1.5 degrees Celsius. The warmer the earth gets, the greater the fallout in terms of rising sea levels, extreme storm events, and ecological disruption, all of which have repercussions on global health, security, and stability.

“The worst part of this crisis is that people who are marginalized, who are poor, will suffer 10 times more than those who contributed to this situation,” says SenGupta.

There are three ways to reduce CO₂, he says. The first — government action — can reduce emissions, but that won’t address what’s already in the air.

“The second way is removing it from point sources, places like chimneys and stacks where carbon dioxide is being emitted in huge amounts,” he says. “The good thing about that is you can remove it at very high concentrations, but it only targets emissions from specific sources.”

The newest method is called direct air capture, which, he says, “allows you to remove CO₂ from anywhere, even your own backyard.”

With DAC, chemical processes remove CO₂ from the atmosphere, after which it’s typically stored underground. However, says SenGupta, the technology is limited by its capacity. It can’t capture enough CO2 to overcome the energy cost of running the process.

“If you’re capturing carbon dioxide from a chimney at a plant, the amount of CO₂ in the air can be upwards of 100,000 parts per million,” he says. “At that concentration, it’s easy to remove. But generally speaking, the CO2 level in the air is around 400 parts per million. That’s very high from a climate change point of view, but for removal purposes, we consider that ultra-dilute. Current filter materials just can’t collect enough of it.”

Another challenge with DAC involves storage. After the CO₂ is captured, it’s dissolved, put under pressure, liquified, and typically stored miles underground. A DAC operation must then be located in an area with enough geological storage — and stability. A country like Japan, for instance, can’t pump CO₂ underground because the area is prone to earthquakes.

Seeing a solution in seawater

SenGupta has developed a DAC method that overcomes both the capture problem and the issue of storage.

For the capture problem, he developed DeCarbonHIX — a mechanically strong, chemically stable sorbent (a material used to absorb liquids or gasses) — that contains copper.

“The copper changes an intrinsic property of the parent polymer material and enhances the capturing capacity by 300 percent,” he says. “We showed that for direct air capture from air with 400 parts per million of CO₂, we achieve capacity, meaning capacity is no longer a function of how much carbon dioxide is in the air. The filter will get saturated completely at any concentration, which means you can perform DAC in your backyard, in the middle of the desert, or in the middle of the ocean.”

The ocean is actually SenGupta’s solution to the storage problem. His DAC process starts with air blowing through the filter to capture CO₂. Once the filter is saturated with gas molecules (determined by measuring the amount of gas going into the filter versus coming out of it), seawater is passed through the filter. The seawater converts the carbon dioxide to sodium bicarbonate (you likely know it as baking soda, but lose the visual as we’re talking about a dissolved solution here). The dissolved sodium bicarbonate is then released directly into the ocean, what Sengupta calls “an infinite sink.”

“And it has no adverse impact on the ocean whatsoever,” says SenGupta. “It doesn’t change the salinity at all.”

In fact, he says, the sodium bicarbonate, which is slightly alkaline, may improve the health of the ocean. That’s because elevated levels of CO₂ in the atmosphere have gradually reduced the pH of the ocean, causing acidification. More acidic waters harm the growth and reproduction of marine life like corals and plankton and can create catastrophic collapses in the food chain.

“Sodium bicarbonate may reverse that lowering of pH,” he says.

It’s worth noting, he says, that like existing DAC processes, DeCarbonHIX can also be desorbed with hot water or steam, and pure CO₂ can be recovered, compressed, and stored underground in geological storage.

“In reality, this new filter material offers a dual mode of desorption and sequestration.”

In a study published in Current Biology, Tulane psychology professor Jonathan Fadok, PhD, and postdoctoral researcher Lydia Smith-Osborne looked at two forms of psychosocial stress — social isolation and social instability — and how they manifest themselves based on social rank.

They conducted their research on adult female mice, putting them in pairs and allowing them to form a stable social relationship over several days. In each pair, one of the mice had high, or dominant social status, while the other was considered the subordinate with relatively low social status. After establishing a baseline, they monitored changes in behavior, stress hormones and neuronal activation in response to chronic social stress.

“We analyzed how these different forms of stress impact behavior and the stress hormone corticosterone (an analogue of the human hormone, cortisol) in individuals based on their social rank,” said Fadok, an assistant professor in the Tulane Department of Psychology and the Tulane Brain Institute. “We also looked throughout the brain to identify brain areas that are activated in response to psychosocial stress.”

“We found that not only does rank inform how an individual responds to chronic psychosocial stress, but that the type of stress also matters,” said Smith-Osborne, a DVM/PhD and the first author on the study.

She discovered that mice with lower social status were more susceptible to social instability, which is akin to ever-changing or inconsistent social groups. Those with higher rank were more susceptible to social isolation, or loneliness.

There were also differences in the parts of the brain that became activated by social encounters, based upon the social status of the animal responding to it and whether they had experienced psychosocial stress.

“Some areas of a dominant animal’s brain would react differently to social isolation than to social uncertainty, for example,” Smith-Osborne said. “And this was also true for subordinates. Rank gave the animals a unique neurobiological ‘fingerprint’ for how they responded to chronic stress.”

Do the researchers think the results can translate to people? Perhaps, Fadok said.

“Overall, these findings may have implications for understanding the impact that social status and social networks have on the prevalence of stress-related mental illnesses such as generalized anxiety disorder and major depression,” he said. “However, future studies that use more complex social situations are needed before these results can translate to humans.”

They published their results on March 30 in Geophysical Research Letters.

The team’s finding could also shed light on another phenomenon: the small shock sometimes felt when touching a metal doorknob. Called spark discharge, it occurs when a voltage difference is created between a body and a conductor. In a series of lab experiments in the 1960s, scientists discovered that spark discharges produce X-rays — just as lightning does. More than 60 years later, scientists are still conducting lab experiments to better understand the mechanism underpinning this process.

Lightning consists in part of relativistic electrons, which emit spectacular high-energy bursts of X-rays with tens of mega electron-volt energies called terrestrial gamma-ray flashes (TGFs). Researchers have created simulations and models to explain the TGF observations, but there is a mismatch between simulated and actual sizes, according to lead author Victor Pasko, Penn State professor of electrical engineering. Pasko and his team mathematically modeled the TGF phenomenon to better understand how it can occur in observed compact space.

“The simulations are all very big — usually several kilometers across — and the community has difficulty reconciling this right now with actual observations, because when lightning propagates, it’s very compact,” Pasko said, explaining that lightning’s space channel is typically several centimeters in scale, with electric discharge activity producing X-rays expanding around tips of these channels up to 100 meters in extreme cases. “Why is that source so compact? It’s been a puzzle until now. Since we’re working with very small volumes, it may also have implications for the lab experiments with spark discharges underway since the 1960s.”

Pasko said that they developed the explanation for how an electric field amplifies the number of electrons, driving the phenomenon. The electrons scatter on individual atoms, which constitute the air, as they experience acceleration. As the electrons move, most of them go forward as they gain energy and multiply, similar to a snow avalanche, allowing them to produce more electrons. As the electrons avalanche, they produce X-rays, which launch the photons backward and produce new electrons.

“From there, the question we wanted to answer mathematically was, ‘What is the electric field you need to apply in order to just replicate this, to launch just enough X-rays backwards to allow amplification of these select electrons?'” Pasko said.

The mathematical modeling established a threshold for the electric field, according to Pasko, which confirmed the feedback mechanism that amplifies the electron avalanches when X-rays emitted by the electrons travel backward and generate new electrons.

“The model results agree with the observational and experimental evidence indicating that TGFs originate from relatively compact regions of space with spatial extent on the order of 10 to 100 meters,” Pasko said.

In addition to describing high-energy phenomena related to lightning, Pasko said the work may eventually help to design new X-ray sources. The researchers said they plan to examine the mechanism using different materials and gases, as well as different applications of their findings.

The other authors on the paper are Reza Janalizadeh, a postdoctoral scholar in the Penn State Department of Electrical Engineering; Sebastien Celestin of the University of Orleans in Orleans, France; Anne Bourdon, of Ecole Polytechnique in Palaiseau, France; and Jaroslav Jansky of the University of Defense in Brno, Czechia.

The National Science Foundation funded this work.

New research led by Penn State reveals that the stem region of the spike protein became progressively tighter over time, and the team thinks this likely improved the virus’s ability to transmit through nasal droplets and infect host cells once in the body. The team said the stem region of the protein that emerged in the most recent Omicron variants is as rigid as it can get, which could mean that newer vaccines may be effective for longer than the ones that targeted the original variant.

“We wanted to see how the spike protein morphed structurally as it evolved from the original wild-type strain of the virus, through the alpha, delta and most recently Omicron variants,” said Ganesh Anand, associate professor of chemistry and of biochemistry and molecular biology, Penn State. “We found that the spike protein was initially more flexible at the stem region, which is where the spike protein is bundled together, but over time, mutations caused the protein to become progressively tighter and more rigid, and we think it’s now as rigid as it can get. This is important because it means that vaccines that are developed to target the current variant with these rigid spike proteins are likely to be effective for much longer than previous vaccines against the more flexible wild-type strain.”

To study how the spike protein changed with each of the new variants, the team studied the virus in vitro (in a test tube) using a technique called amide hydrogen/deuterium exchange mass spectrometry.

Anand explained that the SARS-CoV-2 spike protein is composed of three chain molecules called monomers that are bound together to form a trimer. The spike protein is made up of two subunits, an S1 and S2 subunit. The S1 subunit contains a receptor binding domain while the S2 subunit contains the stem region responsible for bundling the trimer.

“It is analogous to a tree, with the stem forming the trunk and the receptor binding domain forming the branches,” said Anand.

The team’s results, which published in the journal eLife, revealed that the spike protein stem first became more rigid with the D614G mutation, which is common to all SARS-CoV-2 variants. The stem became progressively more twisted with the emergence of new mutations in subsequent variants, and the Omicron BA.1 variant showed the largest magnitude increase in stabilization relative to preceding variants.

Why would the virus benefit from a tighter core?

“We did not study the virus in patients, so we cannot determine if the changes we observed in the spike protein directly affected the newer variants such as Omicron’s ability to transmit more readily; however, we can say that the changes likely made the virus more fit, which could translate to better transmission,” said Anand. “A tighter core could likely make the virus more stable in nasal droplets and faster at binding to and entering host cells. So, for example, what initially took about 11 days to develop an infection after exposure now takes only about four days.”

Anand noted that one of the reasons the vaccines have not been able to fully neutralize the virus is because they were generated against the spike protein of the original wild-type variant.

“The latest bivalent booster — which targets newer variants — helps, but people who never got this booster aren’t receiving this more targeted protection,” he said. “Future vaccines that focus specifically on Omicron are likely to be effective for longer.”

Finally, Anand said that the spike protein has now become so tightly twisted that it is unlikely to structurally change further at the stem region.

“There are limits to how much it can tighten,” he said. “I think that we can have some cautious optimism, in that we’re not going to continuously have variants emerging, at least tightening is not going to be a mechanism.”

Other Penn State authors on the paper include chemistry graduate students Sean Braet, Theresa Buckley and Varun Venkatakrishnan. Kim-Marie Dam, postdoctoral research fellow, and Pamela Bjorkman, assistant professor of biology and biological engineering, Caltech, also are authors.