Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientist uses mass spectrometer to weigh virus particle, von Willebrand factor

27.08.2007
With unprecedented sensitivity, Carnegie Mellon University’s Mark Bier has characterized large viral particles and bulky von Willebrand factors using a novel mass spectrometer. These exciting results may lead to new biological discoveries and represent a step closer to rapid disease diagnosis using mass spectrometry.

“This is a new frontier in mass spectrometry research,” said Bier, associate research professor and director of the Center for Molecular Analysis in the Department of Chemistry in the Mellon College of Science. “We anticipate that this work will help to advance research in proteomics, virology, molecular biology and nanotechnology.” Bier will present his research Thursday, Aug. 23 at the 234th national meeting of the American Chemical Society in Boston.

Mass spectrometers, which separate molecules based on their mass-to-charge ratio, can help researchers identify compounds based on their unique mass and are routinely used to determine the weight, structure and amount of small molecules or fragments of molecules. Conventional instruments, however, are not equipped to sensitively characterize large molecules over 150 kiloDaltons (a measure of mass) at a low-charge state.

Using a Macromizer™ mass spectrometer, Bier’s group successfully analyzed the outer shell of the HK97 virus. They collected a mass spectrum of the mature protein shell, which weighs 12.9 megaDaltons (12,900 kiloDaltons) and the uncleaved protein shell (17.7 megaDaltons), which revealed an unprecedented 30+ positive charges. They also collected an improved mass spectrum of a von Willebrand factor (0.2 to 1.1 megaDaltons), a protein complex in blood necessary for proper coagulation. The ability to directly mass-analyze these heavy biological molecules intact and at a low-charge state represents a new level of analysis previously unattainable using conventional detector technology, according to Bier.

Many biological molecules are too big to be analyzed efficiently at low-charge states using current mass spectrometers, so most scientists break proteins down into smaller fragments before analyzing them in the mass spectrometer. Although an effective and powerful technique, this bottom-up approach typically takes days to complete and does not allow scientists to use mass spectrometers to directly study many large, intact proteins and other macromolecular complexes.

Bier conducted his studies using a top-down approach of the intact complex using a cryodetector-based MALDI TOF mass spectrometer (Macromizer) equipped with 16 superconducting tunnel junctions. Carnegie Mellon houses the only two of these instruments in the U.S. Bier’s group can use the Macromizer to measure the molecular weight of a large, intact protein or a protein complex in a matter of seconds. Because it can measure intact protein complexes, this approach also avoids the sample loss that typically occurs during the bottom-up approach.

“Our results are a first step toward our ultimate goal — to identify a virus, clotting factor or any type of large biological molecule by just weighing it or its gas-phase-generated fragments,” said Bier. “This would provide a rapid clinical tool to diagnose a viral infection or a blood disease, for example.”

Bier is collaborating with Roger Hendrix, a professor of biological sciences at the University of Pittsburgh, who studies how the outer shell of the HK97 virus assembles. Because Hendrix characterizes viral proteins, particles and subunits that are too heavy to study using currently available mass spectrometers, Bier hopes that his data will help them discover new biology. Bier is also collaborating with Dominic Chung, a research professor in the Department of Biochemistry at the University of Washington in Seattle, and Tom Howard, a medical doctor at the VA Greater Los Angeles Healthcare System, who together study von Willebrand factors. “Mark’s analysis by mass spectrometry displays a lot of the details about the composition of normal human plasma von Willebrand factor. This spectrum is truly amazing and very revealing,” Chung said.

Bier’s current work is part of a grant from the National Science Foundation’s (NSF) Biological Infrastructure program, which supports varied activities that provide the infrastructure for contemporary research in biology. With this NSF support, Bier is also building a next-generation heavy ion mass spectrometer.

Amy Pavlak | EurekAlert!
Further information:
http://www.cmu.edu
http://mass-spec.chem.cmu.edu/www-mbier/

Further reports about: Complex Particle Virus Willebrand factor intact mass spectrometer

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 >>>