University of Chicago chemists have demonstrated for the first time how to use a simple laboratory model consisting of only a few chemical reactions to predict when and where blood clotting will occur. The scientists used microfluidics, a technique that allowed them to probe blood clotting on surfaces that mimic vascular damage on the micron scale, a unit of measurement much narrower than the diameter of a human hair.
Although scientists understand what occurs during many of the 80 individual chemical reactions involved in blood clotting, many questions about the dynamics of the entire reaction network remain. Rustem Ismagilov, Associate Professor in Chemistry at the University of Chicago, and graduate students Christian Kastrup, Matthew Runyon and Feng Shen have now developed a technique that will enable scientists to understand the rules governing complex biological reaction networks. They will detail their technique in the online early edition of the Oct. 16-20 issue of the Proceedings of the National Academy of Sciences.
Life and death literally depend on a finely tuned blood-clotting system. "Clotting has to occur at the right place at the right time," Ismagilov said. "A strong, rapid clotting response is essential to stop bleeding at a wound, but such a clotting response at the wrong spot can block blood vessels and can be life-threatening."
In the past, scientists have typically examined the blood-clotting network using flasks containing homogenous mixtures-the test fluids were the same throughout. But the contents of the circulatory system are not homogeneous, said Kastrup, a Ph.D. student in chemistry and the PNAS article's lead author. One of the great virtues of microfluidics technology is its ability to control complex reactions at critical times and locations.
"The blood-clotting system contains both fluids and surfaces in an elaborate spatial environment, where localization of chemicals is very important," he said. Microfluidic technology can address this issue through its ability to control complex reactions at critical times and locations.
In previous work, the Ismagilov group designed a simple laboratory model to simulate blood clotting. In this model, Ph.D. student Runyon and his associates devised three modules that correspond to the three major stages of clotting: production of chemicals that activate clotting, the inhibition of these activators, and formation of the solid clot.
In this model, the scientists used only one chemical reaction in each module instead of the 20-to-30 biochemical reactions that the modules represent. Surprisingly, this simple model adequately reproduced many features of blood clotting.
"There's a long history in chemistry of using simple models to understand more complex behavior," Kastrup said. "Instead of looking at hundreds of equations for blood clotting, we reduced it down to three main equations. From these equations we were able to describe a lot of the dynamics of clotting."
The ability of microfluidics to mimic the flow and geometry of human blood vessels also proved critical.
"We had to use microfluidics to do all of this because that's how we controlled where everything is," Ismagilov said of Runyon's previous work. "It turned out that we got appropriate behavior only if we used geometry similar to those observed in our vascular system. If we changed the geometry to something that didn't look like a biological system, the chemical system couldn't function. So geometry and flow were very important."
In the latest advance, Kastrup used Runyon's model to see if he could predict when clotting would occur in human blood. The team predicted and verified that clotting occurs only at locations of vascular damage larger than a critical size. "Surprisingly, this simple model made correct, quantitative predictions about blood clotting," Kastrup said.
Furthermore, the model provided new details about the dynamics of clotting. A big question in blood-clotting studies is the role of a protein called tissue factor. Can tissue factor exist in blood without the presence of clotting?
"From our experiments we see that it's not the overall concentration of tissue factor that matters, but it's the localization of it that makes a difference," Kastrup explained. That means a high concentration of tissue factor at one location will result in clotting, while the same number of molecules spread farther apart will not.
In the future, chemists might now be able to apply microfluidics to the study of other complex reaction networks that control various biological functions. And in the medical arena, the technique could become a way to perform rapid and detailed diagnostic tests. "We'd love to see that happen," Kastrup said.
Steve Koppes | EurekAlert!
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences