On new lab chip, heart cells display a behavior-guiding ‘nanosense’

Johns Hopkins biomedical engineers, working with colleagues in Korea, have produced a laboratory chip with nanoscopic grooves and ridges capable of growing cardiac tissue that more closely resembles natural heart muscle. Surprisingly, heart cells cultured in this way used a “nanosense” to collect instructions for growth and function solely from the physical patterns on the nanotextured chip and did not require any special chemical cues to steer the tissue development in distinct ways. The scientists say this tool could be used to design new therapies or diagnostic tests for cardiac disease.

Leslie Tung, left, and Andre Levchenko, right, both of the Department of Biomedical Engineering, with Deok-Ho Kim, a doctoral student in Levchenko’s lab, who holds a nanopatterned chip able to cue heart cells to behave like natural heart tissue. Photo: Will Kirk/homewoodphoto.jhu.edu

Leslie Tung, left, and Andre Levchenko, right, both of the Department of Biomedical Engineering, with Deok-Ho Kim, a doctoral student in Levchenko’s lab, who holds a nanopatterned chip able to cue heart cells to behave like natural heart tissue. Photo: Will Kirk/homewoodphoto.jhu.edu

The device and experiments using it are described in this week’s online Early Edition issue of Proceedings of the National Academy of Sciences. The work, a collaboration with Seoul National University, represents an important advance for researchers who grow cells in the lab to learn more about cardiac disorders and possible remedies.

“Heart muscle cells grown on the smooth surface of a Petri dish would possess some, but never all, of the same physiological characteristics of an actual heart in a living organism,” said Andre Levchenko, an associate professor of biomedical engineering in Johns Hopkins’ Whiting School of Engineering. “That’s because heart muscle cells—cardiomyocytes—take cues from the highly structured extracellular matrix, or ECM, which is a scaffold made of fibers that supports all tissue growth in mammals. These cues from the ECM influence tissue structure and function, but when you grow cells on a smooth surface in the lab, the physical signals can be missing. To address this, we developed a chip whose surface and softness mimic the ECM. The result was lab-grown heart tissue that more closely resembles the real thing.”

Levchenko said that when he and his colleagues examined the natural heart tissue taken from a living animal, they “immediately noticed that the cell layer closest to the extracellular matrix grew in a highly elongated and linear fashion. The cells orient with the direction of the fibers in the matrix, which suggests that ECM fibers give structural or functional instructions to the myocardium, a general term for the heart muscle.” These instructions, Levchenko said, are delivered on the nanoscale—activity at the scale of one-billionth of a meter and a thousand times smaller than the width of a human hair.

Levchenko and his Korean colleagues, working with Deok-Ho Kim, a biomedical engineering doctoral student in Levchenko’s lab and the lead author of the PNAS article, developed a two-dimensional hydrogel surface simulating the rigidity, size and shape of the fibers found throughout a natural ECM network. This biofriendly surface made of nontoxic polyethylene glycol displays an array of long ridges resembling the folded pattern of corrugated cardboard. The ridged hydrogel sits upon a glass slide about the size of a U.S. dollar coin. The team made a variety of chips with ridge widths spanning from 150 to 800 nanometers, groove widths ranging from 50 to 800 nanometers and ridge heights varying from 200 to 500 nanometers. This allowed researchers to control the surface texture over more than five orders of magnitude of length.

“We were pleased to find that within just two days the cells became longer and grew along the ridges on the surface of the slide,” Kim said. Furthermore, the researchers found improved coupling between adjacent cells, an arrangement that more closely resembled the architecture found in natural layers of heart muscle tissue. Cells grown on smooth, unpatterned hydrogels, however, remained smaller and less organized, with poorer cell-to-cell coupling between layers. “It was very exciting to observe engineered heart cells behave on a tiny chip in two dimensions like they would in the native heart in three dimensions,” Kim said.

Collaborating with Leslie Tung, a professor of biomedical engineering in the Johns Hopkins School of Medicine, the researchers found that after a few more days of growth, cells on the nanopatterned surface began to conduct electric waves and contract strongly in a specific direction, as intact heart muscle would. “Perhaps most surprisingly, these tissue functions and the structure of the engineered heart tissue could be controlled by simply altering the nanoscale properties of the scaffold. That shows us that heart cells have an acute ‘nanosense,’” Levchenko said.

Johns Hopkins researchers developed this chip to culture heart cells that more closely resemble natural cardiac tissue. Photo: Will Kirk/homewoodphoto.jhu.edu

Johns Hopkins researchers developed this chip to culture heart cells that more closely resemble natural cardiac tissue. Photo: Will Kirk/homewoodphoto.jhu.edu

“This nanoscale sensitivity was due to the ability of cells to deform in sticking to the crevices in the nanotextured surface and probably not because of the presence of any molecular cue,” Levchenko said. “These results show that the ECM serves as a powerful cue for cell growth, as well as a supporting structure, and that it can control heart cell function on the nanoscale separately in different parts of this vital organ. By mimicking this ECM property, we could start designing better-engineered heart tissue.”

Looking ahead, Levchenko said that he anticipates that engineering surfaces with similar nanoscale features in three dimensions, instead of just two, could provide an even more potent way to control the structure and function of cultured cardiac tissue.

In addition to Kim, Levchenko and Tung, authors on this paper are postdoctoral fellow Elizabeth A. Lipke and doctoral students Raymond Cheong and Susan Edmonds Thompson, all from the Johns Hopkins School of Medicine Department of Biomedical Engineering; Michael Delannoy, assistant director of the Johns Hopkins School of Medicine Microscope Facility Center; and Pilnam Kim and Kahp-Yang Suh, both of Seoul National University.

Tung and Levchenko are affiliated faculty members of the Johns Hopkins Institute for NanoBioTechnology. Thompson is a member of INBT’s Integrative Graduate Education and Research Traineeship in nanobiotechnology. Funding for this research was provided by the National Institutes of Health and the American Heart Association.

Related Web sites

Andre Levchenko’s Lab

Leslie Tung’s Lab

Johns Hopkins Institute for NanoBioTechnology

Story by Mary Spiro

Cell’s ‘cap’ of bundled fibers could yield clues to disease

Newsletter readers! If you are looking for the 2010 NanoBio Symposium story go to: http://inbt.jhu.edu/outreach/symposium
Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled “cap” of thread-like fibers that holds a cell’s nucleus in its proper place. Photo by Will Kirk, Homewoodphoto.jhu.edu.

Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled “cap” of thread-like fibers that holds a cell’s nucleus in its proper place. Photo by Will Kirk, Homewoodphoto.jhu.edu.

It turns out that wearing a cap is good for you, at least if you are a mammal cell.

Researchers from the Johns Hopkins Engineering in Oncology Center have shown that in healthy cells, a bundled “cap” of thread-like fibers holds the cell’s nucleus, its genetic storehouse, in its proper place. Understanding this cap’s influence on cell and nuclear shape, the researchers say, could provide clues to the diagnosis and treatment of diseases such as cancer, muscular dystrophy and the age-accelerating condition known as progeria.

“Under a microscope, the nucleus of a sick cell appears to bulge toward the top, while the nucleus of a healthy cell appears as a flattened disk that clings to the base,” said principal investigator Denis Wirtz, professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center. “If we can figure out how and why this shape-changing occurs, we may learn how to detect, treat or perhaps even prevent some serious medical disorders.”

Scientists have known that misshapen nuclei are an indicator of disease, Wirtz said, but they were not certain how a cell controlled the shape of its nucleus, the structure in mammal cells where genetic material resides. In a study published in the Nov. 10 issue of the Proceedings of the National Academy of Sciences, however, the research team led by Wirtz reported the discovery of a fibrous structure that holds the nucleus in its place. The researchers call this new network structure the perinuclear actin cap.

“In healthy cells, the perinuclear actin cap is a domed structure of bundled filaments that sits above the nucleus, sort of like a net that is tethered all around to the perimeter of the cell membrane,”

Wirtz said. This configuration pushes the nucleus down toward the base of the cell and also creates the distinctive flattened shape of normal cells. Cells with cancer, muscular dystrophy or progeria, however, lack this distinctive cap, allowing the nucleus to float upward toward the top of the cell’s membrane. These diseased cells may appear more rounded and bulbous.

“The cap controls the shape of the nucleus by controlling the shape of the cell itself,” Wirtz said.

The perinuclear actin cap was discovered while the team was trying to find out if cell shape controls nucleus shape. By growing cells on a surface with alternating sticky and non-sticky stripes, the researchers noticed that as cells grew along a sticky stripe, their nuclei elongated as well. Using a confocal microscope — a special kind of microscope that can view an object one “slice” at a time — doctoral student Shyam Khatau was able to reconstruct the cell in three dimensions. By stacking the confocal microscope images together, Khatau, who is affiliated with the Johns Hopkins Institute for NanoBioTechnology, was able to produce short movies showing the 3-D structure of the cells, the nucleus and the perinuclear actin cap. (The movies are online here or below.)

“That’s when we saw the cap,” Khatau said, “and Dr. Wirtz realized we were on to something.”

The cap’s role in disease became evident when Khatau tested cells without the gene to produce lamin A/C, a protein found in the membrane of the nucleus of normal cells but absent in the nuclear membrane of cells from people with muscular dystrophy. Cells without lamin A/C failed to produce the perinuclear actin cap.

“We next plan to study how the cap’s effect on the shape of the nucleus affects what genes the cells express,” said Wirtz.

Khatau, who is pursuing his doctorate in the Department of Chemical and Biomolecular Engineering, is lead author of the journal article.

Additional Johns Hopkins authors on this paper are Wirtz; doctoral student Christopher M. Hale and senior Meet Patel from the Whiting School of Engineering’s  Department of Chemical and Biomolecular Engineering; and Peter C. Searson, a professor in the school’s Department of Materials Science and Engineering. Other co-authors were P. J. Stewart-Hutchinson and Didier Hodzic from the School of Medicine at the Washington University in St. Louis and Colin L. Stewart from the Institute of Medical Biology, Singapore.

This work was funded by the National Institutes of Health and the Muscular Dystrophy Association.

Story by Mary Spiro

PNAS journal article.

Johns Hopkins Engineering in Oncology Center

Johns Hopkins Institute for NanoBioTechnology

Department of Chemical and Biomolecular Engineering

Johns Hopkins nanobio summer internship helps undergrads learn research ropes

Summertime flies by when it is spent hard at work in a laboratory; but the 12 student researchers selected for Johns Hopkins Institute for NanoBioTechnology (INBT) Research Experience for Undergraduates (REU) still had plenty of fun. Here are highlights of their experience working, living, and playing at Johns Hopkins University this summer. INBT’s NanoBio REU is funded by the National Science Foundation.

Ten weeks of intensive research

Nanobio REU 2009: First Row, l-r: INBT ed. prog. coordintor Ashanti Edwards, Olusoji Afuwape. Second Row: Lawrence Lin, Stefanie Gonzalez, Stephanie Naufel, Hannah Wilson, Amber Ortega. Back row: Chao Yin, Steven Bolger, Ranjini Krishnamurthy, Alex Federation, John Jones Molina. (Spiro/INBT)
Nanobio REU 2009: First Row, l-r: INBT ed. prog. coordinator Ashanti Edwards, Olusoji Afuwape. Second Row: Lawrence Lin, Stefanie Gonzalez, Stephanie Naufel, Hannah Wilson, Amber Ortega. Back row: Chao Yin, Steven Bolger, Ranjini Krishnamurthy, Alex Federation, John Jones Molina. (Spiro/INBT)

Each REU student conducted research for 10 weeks in the lab of an INBT affiliated faculty member who served as their principle investigator (PI). Students were mentored by a graduate student or postdoctoral fellow in the faculty member’s lab and developed research projects that could be feasibly completed within this time. Findings were presented at a collaborative poster session. (See section below.)

“When I came to Johns Hopkins, I expected people to be more cutthroat about their work. What I found was that people are very serious about their work, but at the same time they were laid back, approachable and helpful, which made it even better. I would recommend this program to anyone.”  ~Alex Federation, University of Rochester

“I had previously planned to just get my master’s degree and stop, but I had such a great experience that I am now considering getting my PhD.” ~ Ranjini Krishnamurthy, Johns Hopkins University

Beyond the lab

Chao Yin worked at the School of Medicine (Bailey/JHU)
Chao Yin worked at the School of Medicine (Bailey/JHU)

To expose the REU students to concepts and ideas beyond the laboratory, INBT hosted four professional development seminars during June and July. Anyone on campus was welcome to attend these seminars. REU participants had the opportunity to listen to professionals discuss  wide-ranging topics. Talks covered intellectual property, how to market a new technology, how science makes it into the news, and what to expect after graduation. These hour-long talks featured speakers John Fini, director of Intellectual Property for the Homewood schools; Charles Day, senior editor at Physics Today; Tim Weihs, professor of Materials Science and Engineering and co-founder of Reactive NanoTechnologies (makers of NanoFoil®); and Matthew Lesho, Biomedical Engineer with Northrop Grumman Electronic Systems and Hopkins alumnus.

“My lab was great. Everyone was hard working but at the same time they joked around so that made it fun. I enjoyed INBT’s professional development seminars because they gave insight to subjects outside of basic science.”   ~ Chao Yin, Duke University

Unique opportunities

REU student Kayode Sanni, 3rd from left, and assistant prof. Jeff Gray, center, travelled to the RosettaCON 2009 conference in Leavenworth, WA, where Sanni presented his research poster. (Gray Lab/JHU)
REU student Kayode Sanni, 3rd from left, traveled with PI assistant prof. Jeff Gray, center, and the entire Gray Lab to the RosettaCON 2009 conference in Leavenworth, WA, where Sanni presented his research poster. (Gray Lab/JHU)

 

Students integrated fully into the labs where they worked. Research completed by an REU participant could be published on its own, or become part of published work via their PI at some point in the future–and this is a goal.  Principle investigators and mentors work with students to quickly design projects of scientific merit so that research is not merely an exercise, but fulfills the goal of being a “research experience for undergraduates.”  INBT labs to which students are assigned engage in some of the most advanced nanobiotechnology research in the world.  Some students may be able to travel to scientific conferences to present their findings.  Even without this opportunity, however, INBT’s REU participants truly learn what the life of a researcher is like.

Laboratory tours

 

Research undergraduates toured the Molecular Imaging Center at the Johns Hopkins School of Medicine. (Spiro/INBT)
Research undergraduates toured the Molecular Imaging Center at the Johns Hopkins School of Medicine. (Spiro/INBT)

The students had an opportunity to tour the Molecular Imaging Center and Cancer Functional Imaging Core, located in the Broadway Research Building Animal Facility at the Johns Hopkins School of Medicine. The Molecular Imaging Center contains facilities for PET and SPECT scans, MRI and spectroscope, ultrasound, optical imaging, a “faxitron” radiography system and an irradiator. A collection of small research animals used for research also is housed in this building. Elena Artemova, administrative coordinator for the center, provided the students with a comprehensive tour.

Collaborative poster session

At the conclusion of the REU program, participants gathered with other research students from across the John Hopkins University campus for an interdisciplinary research poster session at the School of Medicine. More than 80 students from four divisions, including engineering, medicine, arts and science, and public health, presented posters at this session.

 

Stephanie Naufel and Olusoji Afuwape at collaborative poster session. (Spiro/INBT)
Stephanie Naufel and Olusoji Afuwape at collaborative poster session. (Spiro/INBT)

“I learned a lot and definitely learned how to be a researcher. I gained a better appreciation for the amount of work that goes into each research project.” ~ Stefanie Gonzalez, Milwaukee School of Engineering

“It was challenging and I consider that fun. Originally I was only interested in neuroscience, but through this project, I was exposed to the field of epigenetics so that is something I am willing to pursue. It definitely changed my perception about what I wanted to do.” ~ Olusoji Afuwape, University of Illinois at Chicago

Enjoying life in Baltimore

Baltimore  is a city rich in cultural diversity, and there is always plenty to do.  INBT’s summer nanobio REU students saw the Baltimore Orioles play basebal, enjoyed pizza parties and ice cream socials, and had a chance to try some authentic Maryland steamed crabs. They also got to make friends from different parts of the country who were interested in different disciplines. The REU program provides housing, a stipend, and organized group activities with other summer research program participants so that students have the opportunity to meet people from different backgrounds.

 

Maryland's authentic steamed crabs. (Spiro/JHU)
Maryland’s authentic steamed crabs. (Spiro/JHU)

“INBT’s summer REU program is a great way to have networking opportunities with other students, to be interdisciplinary in your research and to learn about different areas of research that you had not thought about before.” ~ Amber Ortega, New Mexico Institute of Mining and Technology

“Although working in a lab with a principle investigator like Doug Robinson was really intense, it pushed me to my limit and I learned a lot. Also the city aspect was nice since I have lived in a small town all my life. There is a lot of culture in Baltimore and that’s what I like.” ~ Lawrence Lin, Rice University

Meet all of INBT 2009 summer nanobio REU students here.

For more information about the  INBT Nanobio REU, click here.

Story by Mary Spiro

Nano education website features INBT mission, programs

The website TryNano.org now features a comprehensive article on Johns Hopkins Institute for NanoBioTechnology  (INBT) and its mission, programs and outreach.

Visit INBT's profile on TryNano.org.

Visit INBT’s profile on TryNano.org.

The TryNano.org website contains feature articles, links, information boxes, videos, and interviews with professionals focused on research and applications of matter at the nanoscale. Generally, the nanoscale is considered to be dimensions from 1 to 100 nanometers, with 1 nm equal to 10-9m. This site strives to a one-stop resource for students, parents, educators and professionals seeking information about nanoscience and nanotechnology. Trynano.org is sponsored by IBM, IEEE and TryScience.

To check out INBT’s profile on TryNano.org, click here.

Johns Hopkins Institute for NanoBioTechnology updates now on Twitter

Follow INBT on Twitter

For the most up-to-the-minute news on what is happening at Johns Hopkins Institute for NanoBioTechnology (INBT) follow us on Twitter. INBT’s science writer, Mary Spiro, will be tweeting the latest information about the institute’s research, educational programs, newest affiliated faulty members, workshops and events. Follow us at @INBT_JHU or visit the INBT Twitter page.

Baltimore nonprofit partners with INBT to sponsor ‘at-risk’ summer scholars

A stable home and a good education are keys to success that many children take for granted. Two Johns Hopkins faculty members have teamed up with a local nonprofit to make sure two academically capable but life-challenged teens from Baltimore can have these same opportunities. Initiated by Doug Robinson, associate professor of cell biology in the School of Medicine and faculty affiliate of the Institute for NanoBioTechnology (INBT), two young men from Boys Hope Girls Hope of Baltimore participated in summer internships in Johns Hopkins laboratories. INBT financially supported the Boys Hope scholars with stipends.

Matthew Green-Hill and Deepak Kalra working in the Montell Lab (Mary Spiro/INBT)

Matthew Green-Hill and Deepak Kalra working in the Montell Lab (Mary Spiro/INBT)

“The main goal was to immerse them in a scientific lifestyle and culture. Their success was measured in terms of each student’s individual progress,” Robinson says. Robinson hosted scholar Donté Jones; Craig Montell, professor of biological chemistry in the School of Medicine, opened up his lab to Matthew Green-Hill. Jones, a sophomore and Green-Hill, a junior, both attend Archbishop Curley High School.

Unlike other programs that try to help children in troubled circumstances by placing them in court-ordered foster homes, students voluntarily apply to Boys Hope Girls Hope of Baltimore to have access to the services it provides, such as a stable home, tutoring, and counseling. Scholars may live together in an adult-supervised home in Baltimore city, but they don’t have to, says the organization’s executive director Chuck Roth.

Scholars attend local private schools, meet with tutors if they need to, earn a weekly allowance for personal expenses, and receive other types of emotional and financial support as needed. The organization has no legal guardianship of the children, Roth adds. As long as their school responsibilities are met, scholars may visit with their families whenever they wish. Roth emphasizes that scholars don’t have records of misbehavior or crime. “These are kids with good potential and who are motivated. They recognize education as a way out of their circumstances,” he says.

Students typically learn about Boys Hope Girls Hope through their school counselors, teachers, relatives, and even their peers. “One of my best friends got into the program, and I didn’t see him for a week. But then he came back and told me about it,” explains Green-Hill. “I literally was one of those kids who knocked on the door of the Boys Hope house and asked to be accepted. I want to be the first person in my family to go to college,” he adds.

At first Green-Hill joined Boys Hope as a non-residential participant, but his home-life was still unsettled. Between middle school and high school, Green-Hill attended seven different schools and moved between several eastern cities. Once his family settled more permanently in Baltimore, he was able to re-apply and move into the supervised Boys Hope home full-time.

Jones had been truant from school for more than two years before he reached the 7th grade and, by his own account, was headed for a “life on the streets.”

Donte Jones and Cathy Kabacoff in Robinson Lab. (Mary Spiro/INBT)

Donte Jones and Cathy Kabacoff in Robinson Lab. (Mary Spiro/INBT)

“It wasn’t that I didn’t like school,” Jones says, “It was just that no one made me go.” After Jones went to live with his aunt, all that changed. She encouraged him to apply to Boys Hope because she saw his academic potential.

Over the summer, Green-Hill was mentored by doctoral student Deepak Kalra in Montell’s biological chemistry lab at the School of Medicine. Kalra involved Green-Hill in as many components of his research as possible and taught him several molecular biology techniques.

“I found Matt to be very sharp and hard working,” Kalra says. “He kept a good record in his lab notebook. Sometimes when he would come to me with a question, I would be intentionally hard and tell him, ‘Go back and look it up in your notebook!’ After a few moments, he would figure it out.” Undaunted by Kalra’s “tough” mentoring, Green-Hill even came in on the weekends to help in the lab.

“At first I thought I wanted to work with athletes and become an orthopedic surgeon,” says Green-Hill, “but after a summer working in the lab, I also might want to go into research so that I can discover ways to help people heal faster.”

Jones also has his heart set on medicine but intends to study nursing when he graduates from high school. Working with research technician Cathy Kabacoff in the Robinson lab, Jones practiced basic lab skills, such as conducting a restriction enzyme digest and measuring protein concentrations. Because Jones had missed several years worth of school, Kabacoff, a former middle school teacher, also helped him improve his writing and mathematics skills. He developed a study plan to research answers to questions of interest to him, such as “What is the Big Bang Theory?” and “What is DNA?”

“For the last two years I’ve been thinking that I wanted to become a nurse, but I also like the science part; I wouldn’t mind working in a lab,” Jones says. “I am taking biology this school year and think I will be better prepared because of all that we worked on.”

Along with their lab work, Robinson and Montell required that the scholars participate in the weekly journal club meetings of the Post-baccalaureate Research Education Program (PREP).  PREP, a minority outreach program that targets recently graduated minority students with the goal of helping them hone their skills in preparation for application to PhD programs, provides a good source of young role models.

Montell says it was exciting to see how each scholar progressed. “They arrived with different skill sets and with different interests so their experiences have not been the same. But the earlier that you can participate in someone’s career, the more impact you can have. Due to our location in east Baltimore, we have a responsibility to give back to the community and this is one way we can do that,” Montell says.

Both scholars agree their experiences were positive.

“I know that you have to have teamwork in sports to be successful, but I didn’t know that you have to have teamwork in academics to be successful. This is why I like working with this lab,” Jones wrote in a summary report at the conclusion of his internship.

In his summary, Green-Hill wrote, “…I am happy to have been exposed to this field of medicine…it has made an impact on my thoughts of my future career and has also given me the experience that I will need to have for my college laboratory sciences.”

Story by Mary Spiro

For more information:

Doug Robinson’s Lab

Craig Montell’s Lab

Boys Hope Girls Hope of Baltimore

INBT researchers use LEGO to study what happens inside lab-on-a-chip devices

Johns Hopkins engineers are using a popular children’s toy to help them visualize the behavior of particles, cells and molecules in environments too small to see with the naked eye. These researchers are arranging little LEGO pieces shaped like pegs to recreate microscopic activity taking place inside lab-on-a-chip devices at a scale they can more easily observe. These lab-on-a-chip devices, also known as microfluidic arrays, are commonly used to sort tiny samples by size, shape or composition, but the minuscule forces at work at such a small magnitude are difficult to measure. To solve this small problem, the Johns Hopkins engineers decided to think big.

Led by Joelle Frechette and German Drazer, both assistant professors of chemical and biomolecular engineering in the Whiting School of Engineering, the team used beads just a few millimeters in diameter, an aquarium filled with goopy glycerol and the LEGO pieces arranged on a LEGO board to unlock mysteries occurring at the micro- or nanoscale level. Their observations could offer clues on how to improve the design and fabrication of lab-on-a-chip technology. Their study concerning this technique was published in the August 14 issue of Physical Review Letters. Both Drazer and Frechette are affiliated faculty members of Johns Hopkins Institute for NanoBioTechnology.

The idea for this project comes from the concept of “dimensional analysis,” in which a process is studied at a different size and time scale while keeping the governing principles the same. [Read more...]

Quantum dots spot epigenetic markers for early cancer detection

Jeff Wang, an associate professor of mechanical engineering, and biomedical engineering doctoral student Vasudev Bailey examine samples of modified DNA during a new test designed to detect early genetic clues linked to cancer. Photo by Will Kirk

Jeff Wang, an associate professor of mechanical engineering, and biomedical engineering doctoral student Vasudev Bailey examine samples of modified DNA during a new test designed to detect early genetic clues linked to cancer. Photo by Will Kirk

A researcher affiliated with Johns Hopkins Institute for NanoBioTechnology has developed a highly sensitive test using quantum dots to detect external chemical modifications to DNA called methylations. Alterations to DNA that do not involve a change in the genetic code, yet can influence gene expression, fall into the emerging science of epigenetics.

The nanotechnology based test for epigenetic markers could be used as an early detection method for cancer or to determine whether a particular cancer treatments is working or not. The research was performed by INBT affiliated faculty member Jeff Tza-Huei Wang,  an associate professor of mechanical engineering from the Whiting School of Engineering, and Stephen Baylin, deputy director of the Johns Hopkins Kimmel Cancer Center. Their findings were published in the August 2009 issue of Genome Research.  Read the full story from Johns Hopkins University News and Information here.

Additional resources

Visit Jeff Wang’s INBT profile page here.

How DNA methylation affects health.

Podcast: Nanotech method to study cell detachment could lead to improved cancer therapies

Peter Searson

Peter Searson

Cancer spreads from organ to organ when cells break free from one site and travel to another. Understanding this process, known as metastasis, is critical for developing ways to prevent the spread and growth of cancer cells. Peter Searson, Reynolds Professor of Materials Science and Engineering in the Whiting School of Engineering and director of the Institute for NanoBioTechnology, led a team of engineers who have developed a method to specifically measure detachment in individual cells.

The method, which uses lab-on-a-chip technology, allows researchers to observe and record the exact point when a cell responds to electrochemical cues in its environment and releases from the surface upon which it is growing. Better knowledge of the biochemistry of cell detachment could point the way to better cancer therapies. In this “Great Ideas” podcast, Elizabeth Tracey, communications associate for the School of Medicine, interviews Searson about this current research.

“…We know that processes like cell detachment are important in cancer metastasis, where cells become detached from tumors…” Peter Searson

Click here to listen:  Great Ideas Podcast: Peter Searson

Related links:

You can watch a video and read more about Searson’s method of studying cell detachment here.

Peter Searson’s INBT profile page.

This podcast was originally posted to the Johns Hopkins University “Great Ideas” web page. To view the original posting, click here.

Hopkins summer scholar research poster session set for Aug. 4

Dozens of students in summer programs across campus, including 12 students from Johns Hopkins Institute for NanoBioTechnology (INBT) REU program, will display the results of their research efforts during a poster session Tues., Aug. 4 from 4 to 6 p.m. in Turner Concourse at the School of Medicine. REU stands for Research Experience for Undergraduates and is a program funded by the National Science Foundation.

INBT’s highly competitive nanobiotechnology REU program chooses students with excellent academic records who express interest in continuing research in graduate school. The students work with INBT affiliated faculty advisers and graduate student mentors to complete a 10-week research project. The application process for the 2010 REU program will begin in December 2009 and closes in mid February 2010.

Ashanti Edwards, INBT’s senior education program coordinator, says, “We believe that it is beneficial for the students to present their research in the form of a poster. This allows the students to practice communicating their research to a broader audience and prepares them for research poster sessions that they will have in graduate school.”

In 2008,  more than 80 students working in laboratories from across the Johns Hopkins University participated in this poster session. The event is free and open to all students, faculty and staff.

Students from INBT’s summer REU program will present the following posters. REU students’ names are in parentheses following the poster title and authors:

  • A Functional Investigation of Potential Molecular Components in Active DNA Demethylation. Olusoji (Yemi) Afuwape, Junjie Guo, Guo-li Ming.  (Olusoji (Yemi) Afuwape, University of Illinois at Chicago)
  • A Synthetic FGF1 Mimetic Peptide: Studies of FGFR3 Binding and Activation. Alexander Federation. Alexander Federation, Jesse Placone, Fenghao Chen, Kalina Hristova. (Alexander Federation, University of Rochester)
  • Relating ECM Stiffness to Cancer Cell Motility. Ranjini Krishnamurthy, Stephanie Fraley, Denis Wirtz. (Ranjini Krishnamurthy, Johns Hopkins University)
  • Nerve Guide Treatment for PNS Damage in Rats. Amber J. Ortega, Shawn H. Lim, Hai-Quan Mao. (Amber Ortega, New Mexico Institute of Mining and Technology)
  • A silica superparamagnetic method for automated methylation analysis. Chao Yin, Vasudev Bailey, Brian Keeley, Yi Zhang, Stephen Baylin, James Herman, Tza-Huei Wang. (Chao Yin, Duke University)
  • Characterization and Colloidal Stability of Surface Oxidized Single-and Multi-Walled Carbon Nanotubes. Hannah Wilson, Kevin Wepasnick, Howard Fairbrother. (Hannah Wilson, University of Maryland Baltimore County)
  • Characterization of the cell cycle dependency of the actin cap. John A. Jones Molina, Shyam Khatau, Denis Wirtz. (John A. Jones Molina, University of Puerto Rico, Rio Piedras Campus)
  • Functionalizing complex, microfabricated curved structures to selectively pattern fibroblasts in 3D. Stefanie M. Gonzalez, Mustapha Jamal, Elizabeth Cha, David Gracias. (Stefanie Gonzalez, Milwaukee School of Engineering)
  • The Development of Organic Nanobioelectronics for Neural Applications.  Stephanie Naufel, Stephen Diegelmann, John D. Tovar. (Stephanie Naufel, Arizona State University)
  • VEGF and substrate compliance upregulate MMP expression in EPCs in in vitro capillary-like structure formation.  Steven Bolger, Donny Hanjaya-Putra, Sharon Gerecht. (Steven Bolger, Duke University)
  • Effects of Substrate Adhesion on Mechanistic Properties of Cytokinesis. Lawrence Lin, Alexandra Surcel, Doug Robinson. (Lawrence Lin, Rice University)

Related Links:

Meet INBT’s summer 2009 REU students

INBT REU program page