In a collaborative effort, researchers from the University of Connecticut (led by Profs. Yao Lin, VJ Kumar and Xudong Yao) and the University of Illinois at Urbana-Champaign (led by Prof. Jianjun Cheng) have made an advance in the rational design of synthetic polypeptides to develop filament-based hydrogels. The work, conceptualized and realized by the graduate students Tianjian Yang (UConn) and Tianrui Xue (UIUC), has been published in the Journal of the American Chemical Society (JACS) and featured as the cover of the March 6 issue.
Building on the recent advancement of autoaccelerated ring-opening polymerization of amino acid N-carboxyanhydrides (NCAs), this study strategically explores a series of random copolymers comprising multiple amino acids, aiming to elucidate the core principles governing gelation pathways of these purpose-designed copolypeptides. The team found that the selection of amino acids steered both the morphology of fibril superstructures and their assembly kinetics, subsequently determining their potential to form sample-spanning networks. Importantly, the viscoelastic properties of the resulting supramolecular hydrogels can be tailored according to the specific copolypeptide composition through modulations in filament densities and lengths. The findings enhance our understanding of directed self-assembly in high molecular weight synthetic copolypeptides, offering valuable insights for the development of synthetic fibrous networks and biomimetic supramolecular materials with custom-designed properties.
The research was supported by NSF grants awarded to Yao Lin at UConn (DMR 1809497 and 2210590) and Jianjun Cheng at UIUC (CHE 1905097).
A new way to regenerate muscle could help repair the damaged shoulders of millions of people every year. The technique uses advanced materials to encourage muscle growth in rotator cuff muscles. Dr. Cato Laurencin and his team reported the findings in the Proceedings of the National Academy of Sciences (PNAS) August 8th issue.
Tears of the major tendons in the shoulder joint, commonly called the rotator cuff, are common injuries in adults. Advances in surgery have made ever better rotator cuff repairs possible. But failure rates with surgery can be high. Now, a team of researchers from the UConn School of Medicine led by Laurencin, a surgeon, engineer and scientist, reports that a graphene/polymer matrix embedded into shoulder muscle can prevent re-tear injuries.
“Most repairs focus on the tendon,” and how to reattach it to the bone most effectively, Laurencin says. “But the real problem is that the muscle degenerates and accumulates fat. With a tear, the muscle shrinks, and the body grows fat in that area instead. When the tendon and muscle are finally reattached surgically to the shoulder bone, the weakened muscle can’t handle normal stresses and the area can be re-injured again.
Dr. Laurencin along with graduate student Nikoo Shemshaki worked with other UConn Connecticut Convergence Institute researchers to develop a polymer mesh infused with nanoplatelets of graphene. When they used it to repair the shoulders of rats who had chronic rotator cuff tears with muscle atrophy, the muscle grew back. When they tried growing muscle on the mesh in a petri dish in the lab, they found the material seemed to encourage the growth of myotubes, precursors of muscle, and discourage the formation of fat.
“This is really a potential breakthrough treatment for tears of the rotator cuff. It addresses the real problem: muscle degeneration and fat accumulation,” Laurencin says.
The next step in their work is studying the matrix in a large animal. The team looks forward to developing the technology in humans.
This work was funded by NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant No. DP1AR068147 and National Science Foundation Emerging Frontiers in Research and Innovation Grant No. 1332329.
(from left to right) Guangfu Wu, Huijie Li, and Zhengyan Weng, advised by Professor Yi Zhang, are checking an array of graphene field-effect transistors.
In recent years, from H1N1 and now to SARS-CoV-2, global pandemics caused by highly contagious viral species have been threatening human life and putting tremendous pressure on healthcare services as well as the economy. Rapid testing and timely interventions for asymptomatic or mild infections caused by SARS-CoV-2, for example, would enable efficient quarantine of infected patients, thus significantly reducing the spread rate of the virus. Importantly, SARS-CoV-2 is expected to continue in the future fall/winter seasons, when it will coincide with the seasonal outbreak of other infectious respiratory diseases, including those caused by influenza virus and respiratory syncytial virus, which have similar signs and symptoms in the early stages. Considering the overlap in the seasonal peaks, symptoms, and underlying risk factors of these illnesses, having a rapid test to detect and differentiate SARS-CoV-2 from other infectious respiratory viruses will be clinically important.
In response to this clinical need, the Institute of Materials Science and Biomedical Engineering Assistant Professor Yi Zhang led the development of the most sensitive amplification-free SARS-CoV-2 diagnostic platform, the CRISPR Cas13a graphene field-effect transistor. This study, entitled “Amplification-Free Detection of SARS-CoV-2 and Respiratory Syncytial Virus Using CRISPR Cas13a and Graphene Field-Effect Transistors,” was published online on May 12, 2022, in the journal Angewandte Chemie International Edition.
“The key features of viral diagnostics are rapidness and sensitivity,” said Zhang. According to Zhang, most virus detection techniques, including the gold-standard RT-PCR, relies on viral sequence amplification, which can dramatically complicate the detection process and increase the risk of cross-contamination, therefore subject to elevated false-positive rates. However, current amplification-free methods are still limited by compromised sensitivity. “Our work revolutionized the field of amplification-free nucleic acid diagnostics by introducing a biosensing platform with sensitivity comparable with RT-PCR,” he said.
Dr. Yi Zhang
Derived from adaptive immunity in prokaryotes, Nobel-winning clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) technology leverages nucleic acid base pair complementarity between a guide RNA and targeted nucleic acid sequence and affords high target specificity capable of discriminating single mismatches. Recently, several CRISPR/Cas systems, including Cas13a, were found to perform cleavage of nonspecific bystander nucleic acid probes triggered by target detection, known as “collateral cleavage.” Such collateral cleavage demonstrates a multi-turnover behavior, turning a single target recognition event into multiple probe cleavage events, and therefore leads to signal amplification.
“The idea of our biosensor design originates from exploiting the signal amplification by translating CRISPR technology onto an ultrasensitive detection platform,” said Huijie Li, a Ph.D. student in Zhang’s lab; she is also the leading first author of the study. Graphene, as a two-dimensional material, exhibits extraordinary charge carrier mobility and thus high electrical conductivity. Thanks to its atomic thickness, graphene, when constructed into biosensors as a sensing material, is highly sensitive to the interaction with biological analytes. In this study, by immobilizing probes on graphene-based field-effect transistors and allowing Cas13a collateral cleavage of these probes activated by target detection, SARS-CoV-2 down to 1 aM level in both spiked and clinical samples, was successfully detected within a 30 min detection time.
Simply by changing the guide RNA design, CRISPR Cas13a graphene field-effect transistor platform was reconfigured to target respiratory syncytial virus with the same attomolar sensitivity. “As the COVID-19 pandemic wanes, our virus diagnostic tool can be easily adapted to combat the future outbreak of unknown viral species,” Guangfu Wu, a Postdoc in Zhang’s lab; he is the co-first author of this work, said.
This study marks a significant milestone towards our goal of developing an integrated point-of-care biosensing platform for viral diagnostics. “We are aiming to offer patients a fast, ultrasensitive all-in-one tool that can streamline sample treatment and analysis and deliver results without any specialized training,” said Zhengyan Weng, a Ph.D. student in Zhang’s lab; he is also the co-first author of this study.
This research is supported by the University of Connecticut start-up and the National Science Foundation under the award number CBET-2103025. The collaborators of this work include Dr. Xue Gao at Rice University (co-corresponding author), Drs. Kevin D. Dieckhaus and Lori Avery at UConn Health, and Dr. Yupeng Chen in the Department of Biomedical Engineering at UConn.
Professor of Chemistry Rajeswari (Raji) Kasi has accepted an appointment to the editorial board of Macromolecules, a peer-reviewed scientific journal published by the American Chemical Society. The publication was first published in 1968 on a bi-monthly basis but has, over the years, moved from monthly to bi-weekly publication.
Kasi’s research encompasses all aspects of materials design including synthesis of hierarchically structured polymers and polymer-hybrid materials with tailored architecture, functionality, and composition; investigation of self-assembly and structure at various length scales; and evaluation of unique macroscopic material properties. She will serve a three-year term on the editorial board.
Ph.D. student Yi Li in Assistant Professor Wang’s group is actuating multistable, origami-inspired structures using a portable magnet.
MSE Assistant Professor Xueju “Sophie” Wang recently published her article entitled “Tailoring the multi-stability of origami-inspired, buckled magnetic structures via compression and creasing” in Materials Horizons. The study was in collaboration with Professor Teng Zhang at Syracuse University and Professor Halim Kusumaatmaja at Durham University, who led the study’s theoretical work.
According to Wang, the research originates from origami, the ancient art of paper folding. “It has inspired the design of many engineering structures for a wide range of applications, including deployable systems, self-folding machines, reconfigurable metamaterials, and DNA origami,” she says.
A key feature in the design of all these structures is their ability to have multiple stable states. The article lays out the foundation for the rational design of these structures. The work introduces two effective parameters of creasing and compression for tailoring the multistability of origami-inspired structures. Using ribbon structures as an example, a design phase diagram is constructed as a function of the crease number and compressive strain. The results show that the number of distinct stable states can be actively tuned by varying the crease number from 0 to 7 and the strain from 0% to 40%. These two parameters can be easily incorporated in the structure’s design to maximize functionality. Diverse examples were designed and demonstrated, from programmable structure arrays to a biomimetic insect and a soft robot, which can be actuated remotely by magnetic forces. Read the full MSE story.
In a collaborative effort, researchers from the University of Connecticut (led by Profs. Yao Lin, VJ Kumar and Xudong Yao) and the University of Illinois at Urbana-Champaign (led by Prof. Jianjun Cheng) have made an advance in the rational design of synthetic polypeptides to develop filament-based hydrogels. The work, conceptualized and realized by the graduate students Tianjian Yang (UConn) and Tianrui Xue (UIUC), has been published in the Journal of the American Chemical Society (JACS) and featured as the cover of the March 6 issue.
