Nanowires Deliver Biochemical Payloads to One Cell Among Many

Imagine being able to drop a toothpick on the head of one particular person standing among 100,000 people in a sports stadium. It sounds impossible, yet this degree of precision at the cellular level has been demonstrated by researchers affiliated with The Johns Hopkins University Institute for NanoBioTechnology. Their study was published online in June in Nature Nanotechnology.

Arrow points to nanowire placed on cell surface. (Image: Levchenko/Chien labs)

The team used precise electrical fields as “tweezers” to guide and place gold nanowires, each about one-two hundredth the size of a cell, on predetermined spots, each on a single cell. Molecules coating the surfaces of the nanowires then triggered a biochemical cascade of actions only in the cell where the wire touched, without affecting other cells nearby. The researchers say this technique could lead to better ways of studying individual cells or even cell parts, and eventually could produce novel methods of delivering medication.

Indeed, the techniques not relying on this new nanowire-based technology either are not very precise, leading to stimulation of multiple cells, or require complex biochemical alterations of the cells. With the new technique the researchers can, for instance, target cells that have cancer properties (higher cell division rate or abnormal morphology), while sparing their healthy neighbors.

“One of the biggest challenges in cell biology is the ability to manipulate the cell environment in as precise a way as possible,” said principal investigator Andre Levchenko, an associate professor of biomedical engineering in Johns Hopkins’ Whiting School of Engineering. In previous studies, Levchenko has used lab-on-a-chip or microfluidic devices to manipulate cell behavior. But, he said, lab-on-a-chip methods are not as precise as researchers would like them to be. “In microfluidic chips, if you alter the cell environment, it affects all the cells at the same time,” he said.

Such is not the case with the gold nanowires, which are metallic cylinders a few hundred nanometers or smaller in diameter. Just as the unsuspecting sports spectator would feel only a light touch from a toothpick being dropped on the head, the cell reacts only to the molecules released from the nanowire in one very precise place where the wire touches the cell’s surface.

With contributions from Chia-Ling Chien, a professor of physics and astronomy in the Krieger School of Arts and Sciences, and Robert Cammarata, a professor of materials science and engineering in the Whiting School, the team developed nanowires coated with a molecule called tumor necrosis factor-alpha (TNF?), a substance released by pathogen-gobbling macrophages, commonly called white blood cells. Under certain cellular conditions, the presence of TNF? triggers cells to switch on genes that help fight infection, but TNF? also is capable of blocking tumor growth and halting viral replication.

Exposure to too much TNF?, however, causes an organism to go into a potentially lethal state called septic shock, Levchenko said. Fortunately, TNF? stays put once it is released from the wire to the cell surface, and because the effect of TNF? is localized, the tiny bit delivered by the wire is enough to trigger the desired cellular response. Much the same thing happens when TNF? is excreted by a white blood cell.

Additionally, the coating of TNF? gives the nanowire a negative charge, making the wire easier to maneuver via the two perpendicular electrical fields of the “tweezer” device, a technique developed by Donglei Fan as part of her Johns Hopkins doctoral research in materials science and engineering. “The electric tweezers were initially developed to assemble, transport and rotate nanowires in solution,” Cammarata said. “Donglei then showed how to use the tweezers to produce patterned nanowire arrays as well as construct nanomotors and nano-oscillators. This new work with Dr. Levchenko’s group demonstrates just how extremely versatile a technique it is.”

To test the system, the team cultured cervical cancer cells in a dish. Then, using electrical fields perpendicular to one another, they were able to zap the nanowires into a pre-set spot and plop them down in a precise location. “In this way, we can predetermine the path that the wires will travel and deliver a molecular payload to a single cell among many, and even to a specific part of the cell,” Levchenko said.

During the course of this study, the team also established that the desired effect generated by the nanowire-delivered TNF? was similar to that experienced by a cell in a living organism.

The team members envision many possibilities for this method of subcellular molecule delivery. “For example, there are many other ways to trigger the release of the molecule from the wires: photo release, chemical release, temperature release. Furthermore, one could attach many molecules to the nanowires at the same time,” Levchenko said. He added that the nanowires can be made much smaller, but said that for this study the wires were made large enough to see with optical microscopy.

Ultimately, Levchenko sees the nanowires becoming a useful tool for basic research. “With these wires, we are trying to mimic the way that cells talk to each other,” he said. “They could be a wonderful tool that could be used in fundamental or applied research.” Drug delivery applications could be much further off. However, Levchenko said, “If the wires retain their negative charge, electrical fields could be used to manipulate and maneuver their position in the living tissue.”

The lead authors for this Nature Nanotechnology article were Fan, a former postdoctoral fellow in the departments of materials science and engineering and in physics and astronomy; and Zhizhong Yin, a former postdoctoral fellow in the Department of Biomedical Engineering. The co-authors included Raymond Cheong, a doctoral student in the Department of Biomedical Engineering; and Frank Q. Zhu, a former doctoral student in the Department of Physics and Astronomy.

Regarding the faculty members’ participation, Chien led the group that developed the electric tweezers technique and collaborated with Levchenko on its biological applications.

The research was funded by the National Science Foundation and the National Institutes of Health.

Johns Hopkins Institute for NanoBioTechnology

Beyond academia and industry

Penelope Lewis, acquisitions editor at the American Chemical Society, spoke at the summer’s second Professional Development Seminar hosted by The Johns Hopkins Institute for NanoBioTechnology (INBT) on June 30 at 11 a.m. in Maryland Hall 110.

Penelope Lewis, acquisitions editor at the American Chemical Society (Photo: Mary Spiro)

Lewis discussed her experience as a scientist making the transition to non-profit, scholarly publishing.

As a PhD candidate, she felt she had only two options: academia or industry. She cautioned against having “too much of a single-minded focus,” as students can get “wrapped up in studying or getting stuck in the lab.” Lewis stressed the importance of having a broad outlook and being involved in a variety of activities to know where one’s true skills and interests lie.

Penelope Lewis advocated for an interactive and investigative approach to understanding career development: “My main piece of advice is to keep your eyes and ears open when considering different careers.” Academic publishing allowed Lewis to combine her interest in writing (she minored in English) with her love of science.

“Being able to communicate your research findings and their significance is such a critical skill. It is necessary not only for securing grants and publishing papers, but also as part of a responsibility that scientists and engineers have to act as good ambassadors for science, and to transfer their excitement and understanding to the public. This is especially important in newer fields like nanotechnology,” she said.

Penelope Lewis has a BS in Chemistry (English Minor) from Indiana University, a Chemistry PhD from Pennsylvania State University, and was a Postdoctoral Research Scientist at Columbia University.

For more information about INBT’s professional development seminars, click here.

Story by Sarah Gubara, Senior, Psychology, Krieger School of Arts and Sciences

ACS Nano editor leads June 30 INBT seminar

Penelope Lewis, acquisitions editor for the journal ACS Nano will lead the next professional development seminar for Johns Hopkins Institute for NanoBioTechnology (INBT) on June 30 at 11 a.m. in Maryland 110. These seminars aim to expand students’ knowledge of issues and ideas relevant to but outside of the laboratory and classroom experience.

Penelope Lewis

Lewis, acquisitions editor of the American Chemical Society’s journal, ACS Nano. Lewis, earned a Ph.D. in chemistry from Penn State University. She will talk about her experience as a scientist moving into the world of academic publishing.

“A career in scholarly publishing can be an interesting and rewarding path for graduate students or post-docs who are looking to move away from the lab bench but still be surrounded by scientific research. In scientific publishing, a doctoral degree or a postdoc is always a great strength and for many positions a requirement. In this talk, I will describe the daily activities involved in working at a non-profit publisher, including the skills and interests that are helpful to succeed in this position,” Lewis said.

All JHU/JHMI and APL faculty, staff and students are invited to attend these free seminars, designed to promote discussion and interaction with scientific and engineering professionals. To find out the location and to RSVP for each seminar, please contact Ashanti Edwards at ashanti@jhu.edu.

Melissaratos opens INBT summer seminar series, June 16

Aris Melissaratos, senior advisor to the president for enterprise development at Johns Hopkins Technology Transfer, will speak at the summer’s first Professional Development Seminar hosted by the Johns Hopkins Institute for NanoBioTechnology (INBT) on June 16 at 11 a.m. in Maryland Hall 110.

A Hopkins’ electrical engineering graduate (‘66), Melissaratos will discuss the importance of technology on academic development and how it affects the standard of living, opportunities of the future, and solves global discrepancies. Melissaratos claims that he has “lots of warnings and advice” to offer, in addition to the benefit of “50 years of industry” experience.

Wednesday’s talk will include excerpts and topics from his new book, Innovation: The Key to Prosperity—Technology and America’s Role in the 21st Century Global Economy, cowritten with N.J Slabbert, which focuses on the translation side of the industry and how to transfer technology. The book “reveals America’s greatest wealth: its scientific and inventive ingenuity” and discusses how to harness and utilize that wealth for its full potential.

Melissaratos is a whiz at developing and financing a product and creating a business around a product. A true product of a research institute, Melissaratos” book “reminds us of the power and adventure of human intelligence,” wrote Gilbert F. Decker, former Science Advisor to the US Secretary of Defense in a review of the book. Topics to look forward to include: redeveloping the American economy to regain supremacy, upping our competitive edge in the global economy, and making up for our country’s lost manufacturing base with research.

Melissaratos has previously served as the vice president of science and technology and chief technology officer at Westinghouse Electronics corporate headquarters in Pittsburgh. He left to join state government in 2003 as Secretary of the Maryland Department of Business and Economic Development. His list of impressive credentials include holding the vice presidency title at Thermo Electron Corp., founding Armel Private Equity Investments, founding the Greater Baltimore Technology Council (co-chair), and serving as vice president of the Maryland Chamber of Commerce.

Four seminars will be held this summer. To attend any of INBT’s Professional Development Seminars, RSVP to Ashanti Edwards at Ashanti@jhu.edu.

For more information: INBT Professional Development Seminar Series, The Aris Institute

Story by Sarah Gubara, Senior, Psychology, Krieger School of Arts and Sciences

Lights! Camera! Science!

 

INBT Web Director Martin Rietveld works on protocol video with PhD student Yu-Ja Huang. (Photo:MSpiro)

Everything about movie making seems so glamorous. From beautiful stars to special effects, making films might appear magical. But actually, when you break it down, shooting a film is not unlike performing experiments in a lab. And, just as reading the script would be far less entertaining as seeing a film, reading a protocol might be confusing until the steps were performed in real life.

That’s the philosophy behind a new effort at Johns Hopkins Institute for NanoBioTechnology: produce short films describing recently published research and the protocols that go with them. The movies are produced collaboratively with INBT’s science writer Mary Spiro, INBT’s Animation Studio director Martin Rietveld, and the scientists and engineers involved.

The INBT Animation Studio already has several research-oriented films to its credit. The animation skills of Rietveld and his student crew have taken us inside a lipid bilayer and carried us along a fiber of collagen. INBT also has produced several video news releases using the talent of students in the annual science communication course.

Recently, however, INBT produced its first film describing a protocol from Nature Methods. Investigators Bridget Wildt, a PhD in materials science and engineering, Peter Searson, Reynolds Professor of Materials Science and Engineering, and Denis Wirtz, Smoot Professor of Chemical and Biomolecular Engineering, served as technical consultants for the production. The research was part of Johns Hopkins Engineering in Oncology Center, of which Wirtz is the director.

Materials science and engineering PhD candidate Yu-Ja Huang performs each step in assembling the Hopkins team’s device and demonstrates how to conduct programmed cell detachment experiments. “Studying cell detachment at the subcellular level is critical to understanding the way cancer cells metastasize,” Searson said. “Development of scientific methods to study cell detachment may guide us to prevent, limit or slow down the deadly spreading of cancer cells.”

Using a draft script developed by Wildt and Searson, Spiro simplified the text further for narrator, materials science and engineering PhD candidate Andrew Wong. Rietveld recorded Huang as he performed the protocol and refined the script further during filming. Viewing the final cut, Wong was able to read the script in a conversational and friendly tone.

You can watch the version of this new protocol video on INBT’s YouTube channel. The film may never earn an Academy Award, but we hope it will help specialists, and even the general public, to understand this unusual and complex procedure.

Related Links:

Check our INBT’s channel on YouTube.

Engineering in Oncology Center

Story by Mary Spiro

INBT welcomes 16 summer nanobio research interns

For 10 weeks this summer, 16 students from universities across the country will join the highly competitive Johns Hopkins Institute for Nanobiotechnology (INBT) Research Experience for Undergraduates (REU). The internship is funded by the National Science Foundation (NSF) and is supported and administered by INBT.

This is the third year of INBT’s REU program, and this group represents the institute’s largest group. Students are being mentored by faculty, graduate students and postdoctoral fellows in INBT affiliated laboratories across Hopkins. At the end of the 10-week research program, they will present their findings at a university-wide collaborative research poster session held with other summer interns from across several divisions.

In November 2009, NSF reported that over the last decade 10 times more white students will have earned doctoral degrees in science and engineering disciplines than minority students. Acknowledging this fact yet resolving not to accept it as status quo, INBT has employed aggressive measures to increase the number of individuals from underrepresented groups who apply to its educational programs.

“The nanobiotechnology REU has been one of the most successful and popular programs for INBT,” says Ashanti Edwards, senior education program coordinator for the institute. “The program has consistently attracted the best and the brightest students interested in research from top universities across the nation. The REU program was launched as a conduit to attract highly talented and motivated research students to pursue academic careers in research, particularly women and minority scholars. The program is highly competitive. For summer 2010, the number of applicants for the 10 slots in the program rose to nearly 500, twice what it had been the year before.”

Johns Hopkins Institute for NanoBioTechnology Summer REU Students. (Photos by Mary Spiro)

INBT’s summer 2010 REU students include pictured from top to bottom, from left to right:

Top row

Joshua Austin, computer science and math major from UMBC, is working with Jeff Gray, associate professor of chemical and biomolecular engineering, Whiting School of Engineering.

Mary Bedard, biochemistry and Spanish major from Elon University, is working with J.D. Tovar, assistant professor of chemistry, Krieger School of Arts and Sciences.

Kameron Black, neuroscience major from the University of California, Riverside, is working in the lab of Ted Dawson, professor of neuroscience, School of Medicine

Obafemi Ifelowo, who majors in molecular biology, biochemistry and bioinformatics at Towson University, is working with Jordan Green, assistant professor of biomedical engineering, School of Medicine.

Second row

Alfred Irungu, mechanical engineering major at UMBC, is working with German Drazer, assistant professor of chemical and biomolecular engineering, Whiting School of Engineering.

Ceslee Montgomery, human biology major from Stanford University, is working in the lab of Doug Robinson, associate professor of cell biology, School of Medicine.

Makeda Moore, biology major from Alabama A & M University, is working with Sharon Gerecht, assistant professor of chemical and biomolecular Engineering, Whiting School of Engineering.

Christopher Ojeda, biomedical engineering major from New Jersey Institute of Technology, is working in the lab of Michael Yu, assistant professor of Materials Science and Engineering, Whiting School of Engineering.

Third row

Katrin Passlack, mechanical engineering and kinesiology major at the University of Oklahoma, is working with Jeff Wang, associate professor of mechanical engineering, Whiting School of Engineering.

Roberto Rivera, chemical engineering major from the University of Puerto Rico, Mayaguez, is working in the lab of Nina Markovic, associate professor of physics, Krieger School of Arts and Sciences.

D. Kyle Robinson, bioengineering major from Oregon State University, is working in the lab of Denis Wirtz, professor of chemical and biomolecular engineering, Whiting School of Engineering. In addition, Kyle is the first REU intern for Johns Hopkins new Engineering in Oncology Center, of which Wirtz is director.

Russell Salamo, biology major from the University of Arkansas, is working with Kalina Hristova, associate professor of materials science and engineering, Whiting School of Engineering.

Bottom row

Quinton Smith, major in chemical engineering with a bioengineering concentration from the University of New Mexico, is working with Sharon Gerecht, assistant professor of chemical and biomolecular engineering, Whiting School of Engineering.

David To, chemistry major from Wittenberg University, is working with assistant professor Hai-Quan Mao in the department of materials science and engineering, Whiting School of Engineering.

Alan Winter, biology systems engineering major from Kansas State University, is working with Professor Peter Searson in the department of materials science and engineering, Whiting School of Engineering. Searson is the director of INBT.

Mary Zuniga, biology major a Northern Arizona University, is working in the lab of David Gracias, associate professor of chemical and biomolecular engineering, Whiting School of Engineering.

Related Links:

Johns Hopkins NanoBio Research Experience for Undergraduates

Professional development seminars kick off with talks on tech transfer, publishing

Aris Melissaratos

UPDATED TIMES AND LOCATIONS

Johns Hopkins Institute for NanoBioTechnology (INBT) will host four free professional development seminars for scientists and engineers this summer. These seminars aim to expand students’ knowledge of issues and ideas relevant to but outside of the laboratory and classroom experience.

Topics include intellectual property, commercialization and entrepreneurship, science journalism and publishing, ‘life after college” and much more. This summer, talks will be held Wednesdays at 11 a.m. on June 16, June 30, July 14 and July 28. Talks on June 16 and June 30 will be held in Maryland 110; talks on July 14 and July 28 will move to Ames 234.

Talks scheduled so far include:

June 16: Aris Melissaratos, senior advisor to the president from Johns Hopkins University Technology Transfer, will discuss what it takes for an research idea to move from bench to the commercial market. Johns Hopkins Technology Transfer is the office that links university researchers and businesses interested in commercializing their inventions.

June 30:  Penelope Lewis, acquisitions editor of the American Chemical Society’s journal, ACS Nano. Lewis, who earned a PhD in Chemistry from Penn State University, will talk about her experience as a scientist moving into the world of academic publishing.

Penelope Lewis

“A career in scholarly publishing can be an interesting and rewarding path for graduate students or postdocs who are looking to move away from the lab bench but still be surrounded by scientific research. In scientific publishing, a doctoral degree or a postdoc is always a great strength and for many positions a requirement. In this talk, I will describe the daily activities involved in working at a non-profit publisher, including the skills and interests that are helpful to succeed in this position,” Lewis said.

All JHU/JHMI and APL faculty, staff and students are invited to attend these free seminars designed to promote discussion and interaction with scientific and engineering professionals. To find out the location and to RSVP for each seminar, please contact Ashanti Edwards at ashanti@jhu.edu.

First annual NCI physical sciences-oncology center investigators’ meeting held

Bryan Smith (Stanford) and Christopher Hale (JHU) shared a PS-OC Young Investigators’ Trans Network Award. (Photo/Mary Spiro)

The First Annual Physical Sciences-Oncology Centers Network Investigators’ Meeting was held April 5-7, at the National Harbor in Washington, D.C. Johns Hopkins Engineering in Oncology Center director Denis Wirtz, professor of chemical and biomolecular engineering,  presented a tutorial on particle tracking, presented a talk on mechanobiology, and chaired a panel discussion on cancer cell mechanics.

In addition, several researchers affiliated with the EOC were awarded Young Investigators Trans-Network Project Awards. Wirtz’s doctoral student Christopher Hale, working with Bryan Smith of Stanford University, was recognized for the poster presentation “Tracking the Mechanics of Cancer in Living Subjects Using Intracellular Nanorheology.” Wirtz’s postdoctoral fellow Daniele Gilkes, working with colleagues at Cornell University, earned accolades for the poster presentation “Synergistic Effects of Hypoxia and Substrate Stiffness on Cancer Cell Force Generation.”

A total of 13 research posters from Johns Hopkins PS-OC were presented at the three-day meeting.

NanoBio Magazine premieres at INBT annual symposium

INBT launches new annual magazine.

As attendees arrived at the Johns Hopkins School of Public Health for the Institute for NanoBioTechnology’s (INBT) fourth annual symposium on April 29, they received the first edition of NanoBio Magazine. The new 32-page publication, which served as both the symposium program and as an attractive way to highlight some of INBT’s research in a more comprehensive way, will be published annually.

NanoBio Magazine, produced under the direction of INBT science writer Mary Spiro and INBT web director Martin Rietveld, showcases articles and photography about the institutes’s research, educational, corporate partnership and outreach programs. Articles were written by INBT staff, as well as students from the science communications course taught by Spiro each January during intersession. Photography came  from students who have participated in INBT supported educational programs, INBT staff, and from affiliated faculty members. The graphic design was created by Y.L. Media, LLC. of Baltimore.

“The magazine represents, in a creative and artistic way, the highly interdisciplinary spirit that is a fundamental mission of INBT,” Spiro said. “It was truly a collaborative effort that pulled content from our affiliated faculty and students  in every division and at every academic level that INBT serves. I hope people will learn what INBT is all about by reading it.”

Printed copies of NanoBio Magazine are available upon request by contacting Mary Spiro at mspiro@jhu.edu. Or, download a PDF version of NanoBio Magazine here:  nanobio-magazine_fordownload

Andrew Wong and Noah Tremblay peruse the first issue of NanoBio Magazine. (Photo by Charli Dvoracek/INBT)

INBT students to teach about self assembly during national science expo

USA Science and Engineering Festival, Oct 23-24

Predoctoral students, faculty and staff affiliated with INBT, including students in INBT’s National Science Foundation funded IGERT program, will help demonstrate the principles of self-assembly to children and adults alike. Participants at the INBT booth will be able to see at the macro scale what happens when materials of various shapes and sizes assemble into more complex structures at the nanoscale. Through a variety of hands-on experiments and by watching a variety of movies and animations about self assembly produced by the INBT Animation Studio, the students hope to be able to share their expertise in science and engineering with the general public.

During the two-day expo, USA Science and Engineering Festival organizers anticipate at least 750 exhibits from more than 350 of the nation’s leading science and engineering organizations including colleges and universities, corporations, federal agencies, museums and science centers, and professional engineering and science societies. Topics represented range from aerospace, green energy, medicine, biotechnology, climatology to robotics, nanotechnology, botany, neuroscience, genetics, and more.

The USA Science & Engineering Festival is the result of the highly successful inaugural San Diego Science FestivalSM held in April 2009 and both are the brainchild of life science and high technology entrepreneur Larry Bock. The festival is hosted by Lockheed Martin and sponsors include Life Technologies Foundation, Clean Technology and Sustainability Industries Organization (CTSI), Larry and Diane Bock, ResMed Foundation, Farrell Family Foundation, Alexandria Real Estate Equities, Northrop Grumman Corporation, Agilent Technologies, Amgen, Celgene Corporation, The Dow Chemical Company, National Institutes of Health, Illumina, You Can Do the Rubik’s Cube, Vertex Pharmaceuticals Inc., Genentech Inc., MedImmune, Sandia National Laboratories, Project Lead The Way (PLTW), K&L Gates, NuVasive Inc., FEI Company, Case Western Reserve University, Silicon Valley Bank, Bechtel Corporation, SpaceX and the National Radio Astronomy Observatory. Media partners include Popular Science and Science Illustrated, New Scientist, EE Times Group, SCIENTIFIC AMERICAN, POPULAR MECHANICS, Forbes Wolfe Emerging Tech Report, FAMILY Magazine and SciVee, Inc.

Additional Information:

Preview of the types of exhibits planned for the National Expo and view a short video of what happened in San Diego here.

For a complete list of sponsors, partners and exhibitors, click here.