Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Exploring the molecular origin of blood clot flexibility

17.01.2007
Well-known protein structure acts as a molecular spring

How do blood clots maintain that precise balance of stiffness for wound healing and flexibility to go with the flow? Researchers at the University of Pennsylvania School of Medicine and the School of Arts and Sciences have shown that a well-known protein structure acts as a molecular spring, explaining one way that clots may stretch and bend under such physical stresses as blood flow.

They report their findings in a Letter in the latest online edition of the Biophysical Journal. This knowledge will inform researchers about clot physiology in such conditions as wound healing, stroke, and cardiovascular disease.

Clots are a three-dimensional network of fibers, made up primarily of the blood protein fibrinogen, which is converted to fibrin during clotting. A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood when tissue is damaged, yet be flexible enough so that it does not block blood flow and cause heart attacks and strokes.

... more about:
»Fibrin »Fibrinogen »stiff

In previous research, senior author John W. Weisel, PhD, Professor of Cell and Developmental Biology, measured the elastic properties of individual fibers and found that the fibers, which are long and very thin, bend much more easily than they stretch, suggesting that clots deform in flowing blood or under other stresses, primarily by the bending of their fibers.

The current research extends those earlier findings to the molecular level, suggesting a way that individual fibers flex - by the unraveling of the three, tightly twisted rod-like regions within fibrinogen molecules, called alpha-helical coiled-coils. The researchers measured this change by pulling engineered strands of fibrinogen molecules using an atomic force microscope. This alpha-helical coiled-coil "spring" is a common motif in protein structure, first identified more than 50 years ago and so its stretchiness may have broader implications in biology and medicine.

By understanding mechanical processes at the molecular level, it may eventually be possible to see how they relate to the mechanical properties of single fibers and a whole clot. This knowledge may enable researchers to make predictions about the function of differently formed fibrin clots in the circulating blood or in a wound. For example, when clots are not stiff enough, problems with bleeding arise, and when clots are too stiff, there may be problems with thrombosis, which results when clots block the flow of blood. First author André Brown, a physics graduate student at Penn, notes that this research is a first step towards understanding the mechanics of the relationship between clot elasticity and disease.

Recent research by other scientists showed that a fibrin fiber could stretch four to five times its original length before snapping. "This is among the most extensible, or stretchy, of polymers that anyone has ever found," says Weisel. "But, how is the stretching happening at a molecular level? We think part of it has to be the unfolding of certain parts of the fibrin molecule, otherwise how can it stretch so much?"

Previous research from senior coauthor Dennis Discher, PhD, Professor in the Physics and Cell & Molecular Biology graduate groups, suggested the possibility that alpha-helical structures in some blood-cell proteins unfold at low levels of mechanical force. But "it wasn't known before that the coiled coil region of the fibrinogen molecule would be the part to unfold under the stress induced by the atomic force microscope," notes Brown.

Once the origins of the mechanical properties of clots are well understood, it may be possible to modulate those properties, note the study authors. "If we can change a certain parameter perhaps we can make a clot that's more or less stiff," explains Weisel. For example, various peptides or proteins, such as antibodies, bind specifically to fibrin, affecting clot structure. The idea would be to use such compounds in people to alter the properties of the clot, so it can be less obstructive and more easily dissolved.

In the future, the researchers will examine other processes at the molecular and fiber levels that may be responsible for the mechanical properties of clots to eventually develop a model that can then be used to predict the effect of changes at one scale on clot properties at other scales. Such a model should be useful for developing prophylactic and therapeutic treatments for many aspects of cardiovascular disease and stroke, suggest the investigators.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

Further reports about: Fibrin Fibrinogen stiff

More articles from Life Sciences:

nachricht Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Could a particle accelerator using laser-driven implosion become a reality?

24.05.2018 | Physics and Astronomy

Hot cars can hit deadly temperatures in as little as one hour

24.05.2018 | Health and Medicine

Complementing conventional antibiotics

24.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>