Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanism Of Blood Clot Elasticity Revealed In High Definition

26.02.2008
Blood clots can save lives, staunching blood loss after injury, but they can also kill. Let loose in the bloodstream, a clot can cause a heart attack, stroke or pulmonary embolism.

A new study reveals in atomic detail how a blood protein that is a fundamental building block of blood clots gives them their life-enhancing, or life-endangering, properties.

The study, conducted by researchers at the University of Illinois and the Mayo College of Medicine, appears in the journal Structure.

Fibrinogen molecules form elastic fibers, the main material of blood clots. When a blood vessel is ruptured, signaling proteins in the blood convert fibrinogen into its active form, called fibrin. Fibrin molecules link together in a scaffold of fibers that seals the vesicle. Cells in the blood, such as red blood cells, fill the gaps.

... more about:
»Fibrinogen »Lim »Molecular »blood »clot »elastic »extension

Fibrinogen is highly elastic, able to reversibly stretch to two or three times its original length.

“Once they’re formed, blood clots have to be elastic because they have a mechanical function to withstand blood pressure,” said Klaus Schulten, holder of the Swanlund Chair in Physics at Illinois.

Understanding what gives fibrinogen its flexibility could help in the design of drugs to enhance their function, he said.

“We investigated what makes blood clots elastic,” said Eric Lee, a graduate research assistant and student in the M.D./Ph.D. program at Illinois. “How do we make them easier to break up or make them less likely to rupture?”

Bernard Lim, a cardiologist at Mayo and an expert on the science of blood clots, contacted Schulten’s group in 2006 for help with a puzzling finding. Lim had conducted a series of experiments using atomic force microscopy to measure the amount of force required to stretch individual fibrinogen molecules.

After dozens of trials, Lim had come up with a “force extension curve” that showed how the fibrinogen molecule behaved when it was stretched. His data indicated that the fibrinogen molecule elongates in a sequential fashion, with three distinct phases. But he could not tell which parts of the fibrinogen molecule were involved.

Fibrinogen is a symmetrical molecule, containing a central region connected to two end regions by long, interweaving coiled chains, called alpha helices. These “coiled coils” were believed to give the molecule its elasticity. But how?

The Illinois team used a computational approach to tackle the mystery. Using steered molecular dynamics (SMD), they modeled the behavior of every atom of the fibrinogen molecule as it was stretched. The computation involved more than a million atoms, and required six months to complete.

The resulting simulation ( see movie) generated a force extension curve that matched the one Lim had produced.

“This was an incredibly strong piece of evidence that what (Lim) saw wasn’t just in the eye of the beholder, but he saw really a property of the protein,” Schulten said.

The simulation also showed in molecular detail how the fibrinogen molecule responded to stretching. Each phase in the force extension curve corresponded directly with a distinct set of events in the elongation of the molecule.

“The simulations revealed that … the extension occurs in a specific and orderly pattern, with distinct regions within the coiled-coil unraveling before others,” the authors wrote.

Lim had also demonstrated that changes in calcium levels or in the pH (acidity) of a blood clot could alter fibrinogen elasticity, a finding that could influence the design of pharmaceutical agents.

“By understanding what happens at the molecular level, you can understand where to target drugs,” Lee said.

This study points to the efficacy of combining molecular dynamics simulations with experimental data on actual molecules, Schulten said. This is proving to be an effective way to get to the heart of molecular behavior, he said.

Simulations can test important, but potentially ambiguous, experimental findings, Schulten said. “And we can see (the behavior of the molecule) in chemical detail, in atomic detail. We see the full chemistry of this mechanical process.”

Schulten directs the theoretical and computational biophysics group at the Beckman Institute for Advanced Science and Technology.

Editor’s note: To reach Klaus Schulten, call 217-244-1604; e-mail: schulten@uiuc.edu.

Klaus Schulten | University of Illinois
Further information:
http://www.uiuc.edu

Further reports about: Fibrinogen Lim Molecular blood clot elastic extension

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>