Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pinpoint Precision: Delivering a Biochemical Payload to One Cell

08.07.2010
Imagine being able to drop a toothpick on the head of one particular person standing among 100,000 people in a 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.

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-alpha), a substance released by pathogen-gobbling macrophages, commonly called white blood cells. Under certain cellular conditions, the presence of TNF-alpha triggers cells to switch on genes that help fight infection, but TNF-alpha also is capable of blocking tumor growth and halting viral replication.

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

Additionally, the coating of TNF-alpha 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-alpha 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 author for the Nature Nanotechnology article was Fan, a former postdoctoral fellow in the departments of Materials Science and Engineering and Physics and Astronomy. Additional authors included Zhizhong Yin, a former postdoctoral fellow in the Department of Biomedical Engineering; 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. The research was funded by the National Science Foundation and the National Institutes of Health.

Brief videos available; contact Mary Spiro

Related links:
Johns Hopkins Institute for NanoBioTechnolgy: http://inbt.jhu.edu
Department of Material Science and Engineering: http://materials.jhu.edu/
Department of Biomedical Engineering: http://www.bme.jhu.edu/

Mary Spiro | Newswise Science News
Further information:
http://www.jhu.edu/

More articles from Life Sciences:

nachricht A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Quantum bugs, meet your new swatter

20.08.2018 | Information Technology

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>