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May 14, 2015

Research Notes

Gel that changes shape could make malleable robot

For decades, robots have advanced the efficiency of human activity. Typically, however, robots are formed from bulky, stiff materials and require connections to external power sources; these features limit their dexterity and mobility. But what if a new material would allow for development of a so-called soft robot that could reconfigure its own shape and move using its own internally generated power?

By developing a new computational model, researchers at the Swanson School of Engineering have designed a synthetic polymer gel that can use internally generated chemical energy to undergo shape-shifting and self-sustained propulsion. Their research, “Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion,” was published in Scientific Reports, a journal of Nature.

The authors are Anna C. Balazs, distinguished professor of chemical and petroleum engineering and the Robert v. d. Luft Professor, and Olga Kuksenok, also a faculty member in chemical and petroleum engineering.

Said Balazs: “Movement is a fundamental biological behavior, exhibited by the simplest cell to human beings. It allows organisms to forage for food or flee from prey. But synthetic materials typically don’t have the capability for spontaneous mechanical action or the ability to store and use their own energy, factors that enable directed motion. Moreover in biology, directed movement involves some form of shape changes, such as the expansion and contraction of muscles. So we asked whether we could mimic these basic interconnected functions in a synthetic system so that it could simultaneously change its shape and move.”

As a simple example in nature, Balazs and Kuksenok use the single-celled organism euglena mutabilis, which processes energy to expand and contract its shape in order to move. To mimic the euglena’s mobility, they looked to polymer gels containing spirobenzopyran (SP), since these materials can be morphed into different shapes with the use of light, and to Belousov-Zhabotinsky (BZ) gels, a material first fabricated in the late 1990s that not only undergoes periodic pulsations but also can be driven to move in the presence of light.

Said Kuksenok: “The BZ gel encompasses an internalized chemical reaction so that when you supply reagents, this gel can undergo self-sustained motion. Although researchers have previously created polymer chains with both the SP and BZ functionality, this is the first time they were combined to explore the ability of SP-BZ gels to change shape and move in response to light.”

As Balazs and Kuksenok noted, these systems are distinctive because they not only undergo self-bending or folding, but also self-propelled motion. The material integrates the powerful attributes of each of the components — the ability of SP-functionalized gels to be “molded” with light and the autonomous mechanical actions of the BZ gels.

According to Balazs, their research produced unexpected results. “Uniform light exposure won’t work. We had to place the light at the right place in order for the gel to move. And if we change the pattern of the light, the gel displays a tumbling motion.

“We also found that if we placed the SP in certain regions of the BZ gel and exposed this material to light, we could create new types of self-folding behavior.”

The next phase of the research will be to combine the patterning of the SP and BZ functionality in the gels with the patterning of the light to expand the polymer’s repertoire of motion.

Balazs added that these SP-BZ gels could enable the creation of small-scale soft robotics for microfluidic devices that can help carry out multistage chemical reactions. “Scientists are interested in designing biomimetic systems that are dissipative — they use energy to perform a function, much like our metabolism allows us to carry out different functions. The next push in materials science is to mimic these internal metabolic processes in synthetic materials and thereby create man-made materials that take in energy, transform this energy and autonomously perform work, just as in biological systems.”

The benefit of using polymer gels instead of metals and alloys to build a robot is that they greatly reduce its mass, improve its potential range of motion and allow for a more graceful device.

“To put it simply, in order for a robot to be able to move more autonomously in a more biomimetic way, it’s better if it’s soft and squishy,” Kuksenok said. “Its ability to grab and carry something isn’t impeded by nonflexible, hard edges. You’d also like its energy source incorporated into the design so that it’s not carrying that as extra baggage. The SP-BZ gel is pointing us in that direction.”


Accelerated brain aging in type 1 diabetes

The brains of people with type 1 diabetes show signs of accelerated aging that correlate with slower information processing, according to findings by Graduate School of Public Health researchers.

The findings indicate that clinicians should consider screening middle-aged patients with type 1 diabetes for cognitive difficulties. If progressive, these changes could influence their ability to manage their diabetes. The study, funded by the National Institutes of Health (NIH), is online and will be published in Neurology.

Said senior author Caterina Rosano, faculty member in the Department of Epidemiology: “The severity of cognitive complications and cerebral small-vessel disease — which can starve the brain of oxygen — is much more intense than we expected, but it can be measured in a clinical setting. Further study in younger patients is needed, but it stands to reason that early detection and intervention — such as controlling cardiometabolic factors and tighter glycemic control, which help prevent microvascular complications — also could reduce or delay these cognitive complications.”

Type 1 diabetes usually is diagnosed in children and young adults and happens when the body does not produce insulin, a hormone that is needed to convert sugar into energy.

Rosano and her co-authors examined brain MRIs, cognitive assessments, physical exams and medical histories of 97 people with type 1 diabetes and 81 of their nondiabetic peers.

The people with type 1 diabetes were participants in the Pittsburgh epidemiology of diabetes complications study, an ongoing investigation led by Pitt epidemiologist and study co-author Trevor Orchard, to document long-term complications of type 1 diabetes among patients diagnosed at Children’s Hospital, 1950-80.

The MRIs showed that 33 percent of the people with type 1 diabetes had moderate to severe levels of white matter hyperintensities (markers of damage to the brain’s white matter, present in normal aging and neurological disorders) compared with 7 percent of their nondiabetic counterparts.

On three cognitive tests that measure abilities such as information-processing speed, manual dexterity and verbal intelligence, the people with type 1 diabetes averaged lower scores than those without the condition.

Among only the participants with type 1 diabetes, those with greater volumes of white matter hyperintensities averaged lower cognitive scores than those with smaller volumes, though the difference was less pronounced.

The associations held even when the researchers adjusted for high blood pressure and glucose control, which are conditions that can worsen diabetes complications.

The study identified signs of nerve damage, such as numbness or tingling in extremities, as a risk factor for greater volumes of white matter hyperintensities.

Said lead author Karen A. Nunley, postdoctoral fellow in the neuroepidemiology program: “People with type 1 diabetes are living longer than ever before, and the incidence of type 1 diabetes is increasing annually. We must learn more about the impact of this disease as patients age. Long-term studies are needed to better detect potential issues and determine what interventions may reduce or prevent accelerated brain aging and cognitive decline.”

Additional Pitt authors on this study were Christopher M. Ryan, Howard J. Aizenstein, J. Richard Jennings, John Ryan, Janice C. Zgibor, Robert M. Boudreau, Tina Costacou and Rachel G. Miller. A VeraLight researcher also contributed.


Brain’s zinc pathway uncovered

A study team led by researchers at the School of Medicine has uncovered a previously unknown pathway the brain uses to fine-tune neural signaling, a pathway that may play a role in Alzheimer’s and other diseases. Their findings appear online in the Proceedings of the National Academy of Sciences.

Scientists have long observed the presence of bubble-like vesicles that contain the neurotransmitter glutamate and zinc at the synapses, specialized contacts among neurons where neurotransmitters are released to propagate electrical signals through the brain.

Glutamate is the major excitatory neurotransmitter in the brain, but the need for synaptic zinc, an essential element that acts as a cofactor for many enzyme and regulatory proteins, has not been understood, noted Thanos Tzounopoulos, faculty member in the auditory research group of the Department of Otolaryngology.

Said Tzounopoulos: “Until now, we haven’t had the ability to quantify or follow zinc when it is released into the synaptic cleft. In this study, we employed new tools to do that and found a pathway that could be important for conditions such as Huntington’s disease and Alzheimer’s.”

A co-investigator at the Massachusetts Institute of Technology developed an agent that fluoresces when it binds zinc, making it possible for the first time to measure zinc levels accurately and track the element’s movements. They also created an agent that blocks zinc activity, thus allowing them to disrupt the metal’s actions to determine its function.

The researchers learned that, indeed, zinc was released from vesicles and diffused from the release site. Surprisingly, it could bind to so-called extrasynaptic glutamate NMDA-type receptors, just like the neurotransmitter glutamate. Whereas glutamate activates these receptors, zinc inhibits them.

“Glutamate acts like an accelerator of neuronal activity, while zinc behaves like a brake that fine-tunes that signal,” Tzounopoulos said. “The receptors that zinc influences are thought to play a role in neurodegenerative diseases, so these findings could open new research avenues in the field.”

The team also included Pitt’s Charles T. Anderson.

The project was funded by NIH.


2-week diet change reduces risk of colon cancer

African-Americans and Africans who swapped their typical diets for just two weeks similarly exchanged their respective risks of colon cancer as reflected by alterations of their gut bacteria, according to an international study led by researchers at the School of Medicine and published online in Nature Communications.

Principal investigator Stephen O’Keefe, faculty member in medicine in the Division of Gastroenterology, Hepatology and Nutrition, observed while practicing in South Africa that his rural patients rarely had colon cancer or intestinal polyps, which can be a cancer precursor. In the Western world, colon cancer is the second-leading cause of cancer death and African-Americans carry the greatest disease burden in the United States.

Said O’Keefe: “The African-American diet, which contains more animal protein and fat and less soluble fiber than the African diet, is thought to increase colon cancer risk. Other studies with Japanese migrants to Hawaii have shown that it takes only one generation of Westernization to change their low incidence of colon cancer to the high rates observed in native Hawaiians. In this project, we examined the impact of a brief diet change on the colon in a controlled setting where we didn’t have to worry about the influence of smoking and other environmental factors on cancer risk.”

After assessment of their in-home diets, 20 African-American and 20 rural South African volunteers ages 50-65 were housed at a Pitt site and at an African lodging facility, respectively. There they ate meals prepared by the researchers using ingredients and cooking techniques typical of the other group.

The team examined fecal and colon content samples, obtained during colonoscopy, of each volunteer at baseline and after the two-week study period. Although the diet change was brief, each group took on the other’s rates of turnover of cells of the intestinal lining, levels of fiber fermentation and markers of bacterial metabolic activity and inflammation associated with cancer risk. In particular, African-Americans experienced an increase in butyrate production, which is thought to play a key role in anticancer pathways. The researchers also noted they removed intestinal polyps from nine of the African-American volunteers, but none were present in the Africans.

According to O’Keefe, increasing the amount of fiber in the diet, from approximately 10 grams to more than 50 for African-Americans in the diet swap, likely led to biomarker changes reflecting reduced cancer risk, but eating less animal fat and proteins also could be helpful.

“These findings are really very good news,” he said. “In just two weeks, a change in diet from a Westernized composition to a traditional African high-fiber, low-fat diet reduced these biomarkers of cancer risk, indicating that it is likely never too late to modify the risk of colon cancer.”

The team included other researchers from Pitt and from Imperial College London, as well as Wageningen University in the Netherlands; University of Helsinki, Finland; University of Illinois, and the University of KwaZulu-Natal in South Africa.

Funding for the study was provided by NIH; the National Institute for Health Research Imperial Biomedical Research Centre, UK; the Academy of Medical Sciences; the Spinoza Award of the Netherlands Organization for Scientific Research; the European Research Council, and the Academy of Finland.

—Compiled by Marty Levine




The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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