INBT Animation Studio: Using Animation to Explore the Nanoworld

Cross section of a Bcl-Xl protein attached to a lipid bilayer. Credit: Ammon Posey/Martin Rietveld/Hill Lab/JHU

Tiny self-assembling metal cubes dance across the screen in a video posted on the Web site of the Johns Hopkins Institute for NanoBioTechnology (INBT). You could read a book—or at least several chapters—on the principles behind how these micro-cubes build themselves up from microscopic, metallic sheets cut by lasers. Or you could watch a one-minute animated video that tells their fantastic story. Most people will opt to watch the video, and now INBT is using animation to explain complex concepts of nanobiotechnology.

The video of the self-assembling cubes is the result of the independent study course Animation in Nanotechnology and Medicine and was produced under the guidance of INBT animation/web director Martin Rietveld. He shares his skills and experience in 2-D/3-D animation with students who sign up for the course and anyone who wants to learn to use this lively medium.

INBT’s animation studio and the independent study course has attracted students from the basic sciences and engineering, the School of Medicine’s Department of Art As Applied to Medicine and The Writing Seminars in the Krieger School of Arts and Sciences, to name a few. Some students understand the science; others are skilled in illustration or other types of visualization. “My job is to try to guide these forces into something that actually produces a movie,“ Rietveld says.

Students who sign up for the course should be aware of the time commitment involved in order to produce a film as well executed as the current productions, Rietveld says. Presently, there are two animated movies on the INBT Web site demonstrating the research of INBT affiliated faculty members. One explains the self-assembling cubes used in the research of David Gracias, assistant professor of chemical and biomolecular engineering in the Whiting School of Engineering, and the other shows the interaction between a protein and a lipid bilayer, based on the work of Blake Hill, associate professor of biology in the Krieger School of Arts and Sciences.

Rietveld recommends that before students start the course, they should be somewhat familiar with animation software. Next, students learn about the science they intend to animate by interviewing the scientists and engineers engaged in the research. Students then shift their attention to production, storyboarding and animation. Eventually, they’ll do post-production and audio work. Projects are completed using INBT’s computers and software. For specific tasks, such as recording video and audio, INBT collaborates with the Digital Media Center and the Center for Educational Resources.

“It can take at least two semesters and students in the course are expected to put in at least 10 hours per week to complete a project,“ Rietveld says. The 3-credit independent study course does not necessarily adhere to a fixed schedule, so students need to have a lot of self-motivation, Rietveld adds.

“It takes a long time to produce something of quality (and) it is difficult to achieve this kind of artistic integrity while maintaining scientific accuracy,“ Rietveld says, “but that is why working in this kind of animation is challenging and fun.“

For more information on INBT’s animation studio or how to register for Animation in Nanotechnology and Medicine (EN 500.495/695), contact Martin Rietveld at


* Channel Forming Protein
* Self Assembling Cubes


* Department of Arts as Applied to Medicine
* Writing Seminars
* Digital Media Center
* Center for Educational Resources
* Animation in Nanotechnology and Medicine

Story by Mary Spiro

Students Lead NanoBio Retreat

Four student presentations, as well as talks by affiliated faculty members, and a poster session highlighted the Oct. 18, fall retreat for the Institute for NanoBioTechnology at Johns Hopkins University. Student presenters included Janice Lin, W. Garrett Jenkinson, Ziqiu (Tommy) Tong and Lamia Wahba. Jenkinson, Lin, Tong, and Wahba are pre-doctoral fellows of INBT’s NanoBio IGERT (Integrative Graduate Education and Research Traineeship), funded by the National Science Foundation. The annual fall retreat gives students from INBT’s educational programs a chance to learn about one another’s research, hear presentations from INBT faculty experts, and network for potential collaborations. Michael Yu, associate professor of Materials Science and Engineering and INBT affiliated faculty member, gave the keynote presentation.

From left to right, Patrick Stahl, Adam Shelley and Janice Lin. Credit: Ashanti Edwards/JHU

Stephen Diegelmann talks with Alfredo Celedon during poster session at INBT’s fall retreat. Credit: Ashanti Edwards/JHU

Students presented research talks during INBT’s fall retreat. Credit: Ashanti Edwards/JHU

From left to right and from the back: Craig Copeland, Stephen Diegelmann, Terrence Dowbrowsky, Garrett Jenkinson, Peter Searson (INBT director), Jesse Placone, Adam Shelley, Patrick Stahl, Craig Schneider, Laura Ensign, Meghan Vellotti, Shyam Khatau, Denis Wirtz (INBT associate director/HHMI program director), Tommy Tong, Alfredo Celedon, Janice Lin, Matt Keuss, Lamia Wahba, Kate Stebe (IGERT program director), and Tania Chan Credit: Ashanti Edwards/JHU

Science Writing, Video Production Courses Tell Nanoscience Stories

Oxidized carbon nanotubes with sorbates. Credit: Ball Lab / JHU

The Institute for NanoBioTechnology (INBT) at Johns Hopkins University strives to be integrative and multidisciplinary. With 170 faculty and more than two dozen graduate students and undergraduates with backgrounds as diverse as physics and computational medicine, the institute has sought to broaden skills and foster collaborations among its student body and its faculty members. That collaboration now extends to the relationship between science and the mass media through a course called Communication for Scientists and Engineers, which aims to give INBT’s graduate students hands-on experience in learning how to communicate complex ideas to non-technical audiences.

Spiro, course instructor and science writer for INBT, knows first hand the important relationship and possible misunderstanding that can occur between scientists and the media.

Scientific ideas, though important for the public to know, are sometimes hard to comprehend or may seem irrelevant to interests of the non-scientist, Spiro explains, and this can make it difficult to convey the significance of scientific investigation to those not engaged in it.

“On the other hand, journalists are looking for novel stories, are under tight deadlines and may have an inaccurate view of the length and complexity of the scientific process,” Spiro says. “Reporters want to hear about the next breakthrough.”

Although the course is not aimed at training INBT’s graduate students to work as reporters, the overall goal is for them to “gain an appreciation for the importance of communicating scientific ideas clearly and to learn a few tools to successfully do that,” she says. With her formal training as both a journalist and a scientist in mind, Spiro designed the course for science and engineering graduate students to understand the basic components of the media such as “learning how to write a press release, giving a press conference, and interviewing each other.”

Spiro taught a course in science writing for scientists and engineers during the January 2008 Intersession. In January 2009, she will teach a new course that focuses on communicating science through video production, requiring students to work in front of and behind the camera. Spiro hopes that in addition to the writing skills the students develop for communicating their ideas to the public, the focus on video in this new course will add a “different dimension to communicating science,” and highlight an additional medium that scientists can use to advance their scientific ideas to the public.

Public relations experts and media professionals also speak to the class. Guest speakers in 2008 included Davide Castelvecchi from Science News; Gail Porter, director of public and business affairs at the National Institute for Standards and Technology; and Joann Rodgers, director of Media Relations and Public Affairs for Johns Hopkins Medicine.

Graduate students in INBT’s fellowship programs are required to take at least one of Spiro’s science communication courses, either the writing course or the video course. This training is considered part of their professional development training. A few of the student articles written during the 2008 science writing course have been posted to INBT’s Web site (see below). Spiro plans to have work produced during the course on video news releases to be posted by spring 2009.

Examples of student writing include:

* Water: More than just a drink.
* Nanoparticle clusters offer surprises for physical chemists.

Story by Jacob Koskimaki, INBT science writing intern and NanoBio IGERT fellow

Unraveling the Mysteries of Physics on the Nanoscale

Faculty Profile: Nina Markovic

Spin-diode with a nanotube quantum dot (QD) poised between a ferromagnetic (blue) and a non-ferromagnetic metal electrode (red and blue). Yellow walls represent contact barriers between the QD and the electrodes. Credit: Christopher Merchant/JHU

Quantum dots (QD)—nanoscale particles that confine electrons and can emit and absorb light—have been studied in lasers, solar paneling, and biomedical therapeutics. Nina Markovic, affiliated faculty member of the Johns Hopkins Institute for NanoBioTechnology (INBT) and assistant professor of physics in the Krieger School of Arts and Sciences, believes this emerging technology will prove important in cancer therapies, energy transmission, and drug delivery.

“Nanocrystal quantum dots are commercially available,“ Markovic says, “but we are developing a novel kind of quantum dots using carbon nanotubes.“

Carbon nanotubes are long and narrow molecules that look like chicken wire made of carbon atoms. Their fascinating electronic, optical and mechanical properties have been extensively studied in the last ten years. Now that their basic properties are better understood, Markovic explains, the next step is to apply them to biomedical applications such as quantum dot therapeutics or diagnostics.

Recently, Markovic began collaborations with INBT affiliated faculty members Justin Hanes, professor in the Department of Chemical and Biomolecular Engineering and Jennifer Sample from the Applied Physics Laboratory. Together they have been investigating nanotube quantum dots for therapeutic purposes. Markovic and Sample have just been awarded a seed grant from INBT to develop this program.

Picture of Nina Markovic
Nina Markovic. Credit: Mary Spiro / JHU

Specifically, Markovic’s group is working on ways to get their nanotube quantum dots to be frequency-specific. This means they will be able to release their contents on demand and be more selectively controlled—an important step in the specific time-release of drugs, and drug delivery regimes.

In addition, Markovic is interested in quantum computing and applying nanotube quantum dot technology to photovoltaic devices. Her group recently studied a film composed of carbon nanotubes and studied their photovoltaic currents in an innovative type of solar cell. Whereas semiconductors are typically used, her idea is to create a structurally different solar cell that may better transmit electrons from the photons it receives from the sun through the photovoltaic effect.

“If light can be more efficiently captured and converted into an electric current, it may revolutionize solar paneling and its use as an efficient renewable energy,“ Markovic says. [See reference.]

Markovic first became fascinated by quantum mechanics when she took a modern physics course as an undergraduate at the University of Zagreb, Croatia. She says she was drawn to its counterintuitive nature and its elegant mathematical language. After completing a post-doctoral fellowship at Harvard University in 2003, Markovic joined the Hopkins physics faculty. In 2004, she was selected as one of the Alfred P. Sloan Fellows. She received the distinguished National Science Foundation’s Faculty Early Career Development Award in 2006, which gave her $500,000 over five years. Markovic enjoys the classroom and teaches thermodynamics and statistical physics. She particularly enjoys teaching the Frontiers of Physics course for non-science majors, which covers all aspects of physics from quantum physics to astrophysics.

To learn more about the Markovic Lab, click here


“Effects of diffusion on photocurrent generation in single-walled carbon nanotube films,“ C. A. Merchant and N. Markovic, Appl. Phys. Lett. 92, 243510 (2008).

Story by Jacob Koskimaki, INBT science writing intern and NanoBio IGERT fellow

Hopkins Engineer, Chemist Examine Impact of Carbon Nanotubes in Aquatic Environments

Oxidized carbon nanotubes with sorbates. Credit: Ball Lab / JHU

Carbon nanotubes (CNTs)—which resemble tiny rolls of chicken wire—are used in electronics, optics and other products because of their unusual strength and electrical conductivity. CNT’s are also being used for drug delivery. But an engineer and a chemist affiliated with the Johns Hopkins Institute for NanoBioTechnology have teamed up to study the ways that nanotubes could transport harmful toxins in aquatic environments.

William Ball, professor of environmental engineering in the Whiting School of Engineering, and Howard Fairbrother, professor of chemistry in the Krieger School of Arts and Sciences, received two separate grants from the National Science Foundation and the Environmental Protection Agency to study the effects of surface oxides on the behavior of carbon nanotubes and their influence on the mobility of contaminants in aquatic environments.

“When people or animals drink—or otherwise process—water that has been contaminated by CNTs, they may receive the toxins as well as the CNTs,“ says Ball. “Retention and toxicity of the CNT-bound chemicals is still unclear, but the retained chemicals and/or the CNTs themselves may cause harm and can also propagate further up the food chain.“

The team will study how the surface chemistry of CNTs-namely the oxygen-containing functional groups (surface oxides) on the nanotubes—influence the material’s ability to grab onto, transport, and release organic and inorganic pollutants and metals in lakes, streams and oceans, making the carbon nanotubes behave like a “Trojan Horse.“

Part of the study will rely on models based on what is already known about the interaction of oxidized CNT surfaces and toxins. In a study published in Environmental Science and Technology in March 2008, Ball and Fairbrother investigated how surface oxides influenced the adsorption of Naphthalene on multi-walled carbon nanotubes (See reference below). Naphthalene is a common ingredient in mothballs, and exposure to high concentrations of the chemical can damage or destroy red blood cells.

In the experimental phase, the team will oxidize fresh CNTs with nitric acid to mimic the modifications used to purify and functionalize this carbon-based material. Next, the CNTs will be added to columns of silica or sand, and solutions containing organic compounds or metal ions will be flowed through. The liquid that flows out the other end of the column will be collected and analyzed. Testing will occur under different pHs and concentrations of dissolved organic matter, to represent aquatic environments.

These results, Ball says, will be further analyzed in light of appropriate theoretical models, as well as to experimental data about the sorption properties of the carbon nanotubes for various chemicals and the surface-surface interactions among and between CNTs and other materials.

To learn more about the participating Labs visit the profiles in the INBT Faculty Finder.

* Ball Lab
* Fairbrother Lab

Influence of Surface Oxides on the Adsorption of Naphthalene onto Multiwalled Carbon Nanotubes. Cho, Hyun-Hee, Smith, Billy A., Wnuk, Joshua D., Fairbrother, D. Howard, and Ball, William P. Environ. Sci. Technol., 42, 8, 2899 – 2905, 2008, 10.1021/es702363e

Story by Mary Spiro

NanoBio Internship Puts Knowledge Into Action

Picture of Steve WuSteve Wu, intern at Liquidia Technologies. Credit: Mary Spiro / JHU

Skills and knowledge learned in the classroom come alive when a student takes on the challenge of a summer internship. That’s what Steve Hu, a junior in chemical and biomolecular engineering at Johns Hopkins University, discovered when he spent ten weeks working at a paid internship offered through a partnership between the Institute for NanoBioTechnology and Liquidia Technologies of Research Triangle Park, N.C.

“It was really important to have a first-hand experience in a corporate and business environment“ Hu says, “The goals of corporate research are different than goals of academic research, and it was interesting to learn about how that worked.“

Hu is no stranger to academic research settings. During the summer following his freshman year, he completed a National Science Foundation REU (Research Experience for Undergraduates) at the University of New Mexico Center for Micro-Engineered Materials. On the Johns Hopkins campus, he has worked in the laboratory of David Gracias, assistant professor of chemical and biomolecular engineering and an INBT affiliated faculty member.

“In an academic lab, you can pursue a question for as long as you want; there are no boundaries,“ Hu says. “But in a corporate setting, you are developing a product to cater to a certain market, so you are more driven by profit. That’s not a bad thing though, because the purpose in both settings is to solve a problem.“

While working at Liquidia, Hu was fabricating and testing the behavior of polymer nanoparticles of various shapes and sizes designed to encapsulate drugs for targeted delivery. “A cylindrically shaped polymer with an aspect ratio of 5:1 would behave in a completely different way than a spherically shaped one,“ Hu says.

He conducted light scatter analyses, ran particle-size distribution tests, and used AFM (atomic force microscopy) to study the nanoparticles. “We wanted to find out what had been created and how it worked, in vitro and in vivo.“

The application process for INBT’s internship at Liquidia was not complex. Hu submitted his resume to INBT, and after an initial internal review, his application was forwarded to representatives at Liquidia who called him to North Carolina for a face-to-face interview. Hu says he fit in well with the laid-back atmosphere of the start-up company and enjoyed the camaraderie of two other interns hired over the summer. Liquidia awarded Hu both housing and a stipend for his living expenses.

Hu says he would encourage others to seek out research opportunities, whether on campus or off. “There are lots of opportunities here at Homewood or at the School of Medicine. There is probably an opportunity for everyone who wants one, so go for it!“

Future nanobio-related internships offered through INBT will be announced on the INBT Web site as they become available, so please check our “announcements“ link on the institute’s home page. Other types of research opportunities may be available through individual academic departments. Please consult your department chair for more information.

To learn more about Liquidia Technologies, go to .

Story by Mary Spiro

Tiny Medical Tool Nets Gracias New Innovator Award

Self assembling cubes and David Gracias. Credit: Gracias Lab/JHU, Will Kirk/HIPS/JHU

David Gracias, Johns Hopkins University assistant professor of chemical and biomolecular engineering at the Whiting School of Engineering, received the prestigious 2008 New Innovator Award from the National Institutes of Health. Gracias, an affiliated faculty member of the Institute for NanoBioTechnology, builds medical tools smaller than a speck of dust. The NIH grant, worth $1.5 million in direct research costs over five years, was awarded September 22, 2008. Gracias was among 31 scientists from universities and institutes throughout the United States selected to receive this year’s New Innovator grants, designed to support novel research projects. Ronald Cohn, Johns Hopkins assistant professor of pediatrics and neurology at the McKusick-Nathans Institute of Genetic Medicine, was also chosen for the award.

“Nothing is more important to me than stimulating and sustaining deep innovation, especially for early career investigators and despite challenging budgetary times,“ NIH Director Elias A. Zerhouni said. “These highly creative researchers are tackling important scientific challenges with bold ideas and inventive technologies that promise to break through barriers and radically shift our understanding.“

Kristina M. Johnson, provost and senior vice president for academic affairs at The Johns Hopkins University, added, “There is keen competition for major awards such as these. We are extremely pleased that the NIH has recognized the fine research being conducted by Ronald Cohn and David Gracias. This financial support will help move them closer to their goals of producing important new medical treatments and tools.“

David Gracias will use his New Innovator award to continue to develop minimally invasive microscale and nanoscale tools and devices for medicine. Microscale tools are designed to perform procedures such as biopsies or to deliver medication at the cellular level; nanoscale tools operate in the realm of proteins and viruses.

A key advantage of the tiny containers and grippers already developed in Gracias’ lab is that they can release drugs and grasp tissue without requiring batteries or a wire connected to an outside power source. Instead, Gracias’ miniaturized tools are moved from afar by magnets and are activated by chemicals or temperature changes.

“Tomorrow’s medical devices will be smart,“ Gracias says. “We want to get rid of the wires and build an entire mobile, miniaturized surgical toolbox, including devices that can access diseased areas that are difficult to reach with the currently available, tethered, minimally invasive tools.“

Gracias has already demonstrated that his prototypes work in lab experiments, and animal testing is under way. With the New Innovators grant, he hopes to advance this research and move closer to the day when physicians will be able to use his tiny tools on patients. “We have some ambitious goals, and there is a lot of work to be done,“ Gracias says. “But if we succeed, the payoff could be enormous. It could give doctors important new tools to help them diagnose and treat medical problems.“

Gracias was raised in Mumbai, India, and earned his undergraduate and master’s degrees in chemistry at the Indian Institute of Technology at Kharagpur. He received his doctorate in physical chemistry at the University of California, Berkeley, and was a post-doctoral fellow at Harvard University before joining the Johns Hopkins faculty in 2003.

Regarding Gracias’ New Innovator Award, Nick Jones, dean of the Whiting School of Engineering, said, “We’re thrilled that David has received this well-deserved recognition. The award acknowledges more than his pioneering work in micro-to-nanoscale tools and devices for medicine. It is also a confirmation of his role as an exceptionally innovative engineer and recognition of the tremendous potential his research holds.“

The New Innovator Award program was launched by NIH in 2007 to support a small group of new investigators who propose bold new approaches that have the potential to produce a major impact on a broad area of biomedical or behavioral research. The program currently supports 61 investigators—30 selected last year and 31 more this year.

David Gracias’ INBT Faculty Home Page

Information about the New Innovator Awards:

Story adapted from original first posted by the Office of News and Information, Johns Hopkins University.


Picture of Mustapha JamalMustapha Jamal. Graduate student in the Nanobio Igert program. Credit: Mary Spiro / JHU

Cells that give rise to connective tissue, known as fibroblasts, promote wound healing and repair following injury or disease. Mustapha Jamal, a PhD student in the NanoBio IGERT with the Institute for NanoBioTechnology at Johns Hopkins University, is using nano- and micro-fabricated structures to direct the growth of fibroblasts. Funded by the National Science Foundation, IGERT stands for Integrative Graduate Education and Research Traineeship.

Jamal works in the lab of David Gracias, assistant professor in the Department of Chemical and Biomolecular Engineering at the Whiting School of Engineering. One aim of the Gracias Lab is to build very small devices and integrated structures (click here for an example), and to study these systems using microscopy and spectroscopy. Expanding the biological research focus of the Gracias Lab has been one of Jamal’s biggest challenges since coming to work at Johns Hopkins.

“When I was an undergraduate, I always had graduate students that I could go to for help if I had a question, but now I am the graduate student managing undergraduates who are looking to me for guidance,“ Jamal says. “I have a whole new appreciation for what those other graduate students did for me!“ In 2007, Jamal earned a BS/MS degree in chemical and biochemical engineering from UMBC (University of Maryland Baltimore County), where he was a Meyerhoff Scholar.

“My advisors in the Meyerhoff Scholarship Program really encouraged me to do undergraduate research,“ Jamal says. “I worked in the Department of Mechanical Engineering at UMBC where I modeled cell deformation.“

This experience has helped Jamal with his work on fibroblasts conducted under the direction of his co-adviser Roselle Abraham, assistant professor of medicine and a cardiologist in the School of Medicine. Both Gracias and Abraham are Hopkins faculty members affiliated with INBT.

Raised in Indiana, Jamal moved to Maryland during high school. He enjoys basketball, soccer, and listening to all types of music. In the future, he says, “I really enjoy research, but I also would like to be a philanthropist so that I could give back to those organizations that have really helped me, such as the Meyerhoff Scholarship Program or the National Society of Black Engineers.“

For more information on the Gracias Lab, click here .

Story by Mary Spiro

Potential Health Impact of Inhaled NanoMetals to be Studied by Multidisciplinary Team at Johns Hopkins

X-ray of lungs. Credit: Clara Natoli / MorgueFile

Every day, everywhere we go, whether we know it or not, we are exposed to nanomaterials—particles with one dimension no bigger than 1/100,000th the width of a human hair. They can be found in cosmetics, sunscreens, pharmaceuticals, fabrics, and in the air we breathe. It is a challenge to measure how often we encounter these ubiquitous bits of next-to-nothingness and what, if any, impact they may have on our health in an open environment. But three Johns Hopkins University researchers affiliated with the Institute for NanoBioTechnology hope to gain some insight on those effects by studying the ability of nanometals to access lung tissues, their potential to trigger pro-inflammatory reactions by cells that line the lung airways, and even the extent to which workers are exposed in a nanomaterials manufacturing setting.

The National Science Foundation awarded nearly $400,000 to faculty members Shyam Biswal, Patrick Breysse, and Justin Hanes for their collaborative investigation on the toxic health effects of nanometal oxides. “Exposure to nanomaterials in occupational settings is measurable, while exposure in non-occupational settings is hard to characterize,“ says Biswal, a toxicologist at the Bloomberg School of Public Health and principal investigator on the project. “The knowledge we gain from these studies will help in understanding the health effects of nanoparticles that we might encounter in everyday situations.“

Breysse directs the division of Environmental Health Engineering in the Department of Environmental Health Sciences in the Bloomberg School of Public Health. Hanes, professor of chemical and biomolecular engineering in the Whiting School of Engineering, is director of Therapeutics for INBT.

When used in consumer products, nanomaterials provide many benefits, and production of items that use nanomaterials is on the rise. The National Science Foundation estimates that 2 million workers will be needed to support nanotechnology industries worldwide within 15 years*. There is already a large body of research on how exposure to metals impacts both humans and animals, linking it to a range of inflammatory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. However, little is understood about the toxic potential of metal oxides manufactured at the nanoscale.

Biswal, Breysse and Hanes plan to look at how workers become exposed to nanomaterials, how they are transported through the body, and then assess any potential adverse health effects. One goal of the project will characterize the basic physical and chemical properties of the engineered nanometal oxides. Another goal will be to determine what size, what type and how much nanometal oxides are found in the exhaled breath of exposed workers.

Biswal says the project is an excellent representation of a multidisciplinary collaboration between experts in exposure assessment, aerosol science, nanotechnology, the protective mucus barrier, and pulmonary molecular toxicology.

“The nanometal particle is not only important from an occupational point of view. We think that what we learn from these particles will help us understand the effect of other nanoparticles to which we all are exposed,“ Biswal adds. “These studies also will develop the knowledge base required for future studies on larger populations exposed to nanometal particles.“

Other collaborators on this research include Biswal’s research associate Rajesh Thimmulappa; Alexendra Stefanik, an industrial hygienist with the National Institute for Occupational Safety and Health who previously conducted research with Breysse; and Jana Keshavan of the U.S. Army’s Edgewood Chemical Biological Center. This current project grew out of a previous study (Toxicological evaluation of nanoparticles in mice model of chronic lung diseases) funded with seed money from INBT.


Story by Mary Spiro

Artificial Collagen Plays More Than a Supporting Role in Cell Growth

Transmission electron micrographs of reconstituted type I collagen fiber from mouse tail tendon after incubation with gold nanoparticles. The white arrows indicate positions of nanoparticles on collagen fibers. Credit: AMS

Faculty Profile: Michael Yu

Collagen, the body’s most abundant protein, serves as a natural scaffold for cells and directs when and where they will grow. Researchers at the Institute for NanoBioTechnology at Johns Hopkins University are discovering new properties and uses for a synthetic molecule that mimics collagen. When used with nanoparticles, this molecule, called collagen mimetic peptide (CMP) could produce detailed images of tumors, detect deadly buildup in arteries, deliver drugs, and improve blood supply to implanted tissues. Several useful properties of CMP are described in a paper by S. Michael Yu, associate professor of materials science and engineering in the Whiting School of Engineering, and Martin Pomper, professor of radiology and oncology at the School of Medicine, and published in the journal Biomacromolecules (June 12, 2008). Both are INBT affiliated faculty members.

“Collagen is a great house for a cell to grow, but there are places where you should not have collagen,“ Yu says. “Tumors or blood clots that can lead to a stroke are primarily made of collagen.“

The research shows for the first time that synthetic collagen binds to natural collagen in an unpurified ex vivo state—that is, in unprocessed natural tissue specimens (The binding of CMP to purified and prepared collagen grown in a Petri dish was previously reported by Dr. Yu). CMP accomplishes this feat by weaving itself into collagen’s rope-like triple helical structure. The study also shows that CMP incorporates into collagen fibers at precise points along each strand.

“The collagen mimetic peptide was able to ‘sneak’ into the natural collagen fibers at regularly spaced intervals where the structure of collagen was more loosely bound,“ Yu says. Using nanoparticles attached to the CMP molecules, the researchers were able to visualize the entry points with transmission electron microscopy. Each entry point appears as an evenly spaced row of black spots along the length of the collagen fiber, like the markings on a ruler.

To test the CMP’s ability to interact with natural collagen on an intact tissue sample, Yu and Pomper attached a molecule that would emit fluorescent light to the end of the synthetic collagen. Then, a solution of fluorescently tagged CMP molecules was used to stain a sample of human liver tissue. The brightly glowing CMP produced an image that was essentially identical to images achieved by staining with collagen-specific antibodies, the most commonly used method to image collagen, Yu says. “That tells us that in a natural system, the collagen mimetic peptide is binding only to the collagen and not to other proteins—and that has never been shown before.“

The tiny nano-sized CMPs also are able to produce images with greater resolution than antibodies, Yu says. “CMP can penetrate tissue that the antibodies, which are at least 20 times larger, cannot.“ Better images give radiologists like Pomper the ability to see accumulations of collagen in places where it should not be.

Finally, the researchers observed that when the environment heats up—to around 37 degrees Celsius or body temperature—CMPs quickly lose their grip on natural collagen and are released. But by making the CMPs chains a little longer, the researchers could control the amount of time the synthetic collagen would remain bound to its natural counterpart. “The longer the chain, the longer CMP tended to stay in place,“ Yu says. This property would allow CMP to be customized for therapeutic or diagnostic purposes—a short one for a quick dose and a long one to deliver a more sustained treatment.

Yu adds that the potential uses for collagen mimetic peptides are limited only by the types of molecules that one is able to attach to them, and he and Pomper have several patents pending on diagnostic or therapeutic applications. With nanoparticles or nanoshells attached, for example, functionalized CMPs could be used for imaging and drug delivery.

“One of the areas we’re working on now is targeted delivery of these functionalized CMPs,“ says Pomper. “The key will be whether we can make them recognize the difference between normal collagen and pathological collagen.“

Synthetic collagen may also be able to improve the chances of survival for engineered tissue implants. Natural collagen contains chemical signals called growth factors that tell cells how and where to grow and direct the formation of blood vessels. Using growth factors that are linked to CMP, Yu is working on creating collagen scaffolds that can tell cells to form organized networks of blood vessels. A paper focused on this research will be published in the September online issue of Biomacromolecules.

But Yu knows that prospect is a long way off.

“Collagen is a very complicated system and we still don’t know a lot about it,“ Yu says. “Using synthetic systems can give you a lot of information and are great for mechanistic studies of cell and scaffold interactions, but eventually many scientists come back to the natural scaffold that Nature has provided, the collagen, when they need to create artificial tissues.“

Collaborating on this work with Yu and Pomper were doctoral students Allen Y. Wang and Xia Mo, from the Department of Materials Science; instructor Catherine Foss, from the Department of Radiology; and master’s student Shirley Leong, from the Department of Chemical and Biomolecular Engineering. The work was funded by the National Institutes of Health and the National Science Foundation.

More Online

Read the entire scientific paper here:

Spatio-Temporal Modification of Collagen Scaffolds Mediated by Triple Helical Propensity. Allen Y. Wang, Catherine A. Foss, Shirley Leong, Xiao Mo, Martin G. Pomper, and Seungju M. Yu. Biomacromolecules, 9 (7), 1755-1763, 2008.

Visit the Yu Lab Web site.

Visit the Pomper Lab Web site.

Story by Mary Spiro