Featured Research

from universities, journals, and other organizations

Penn Researchers Use Laser Tweezers To Study Strength Of Ligand-Receptor Binding

Date:
May 22, 2002
Source:
University Of Pennsylvania Medical Center
Summary:
Using "laser tweezers," researchers at the University of Pennsylvania School of Medicine have measured the strength of the bond between a single integrin molecule on the surface of a platelet and a molecule of fibrinogen, a clotting protein found in the bloodstream. An article detailing their findings was published in the May 14th online early edition of the Proceedings of the National Academy of Sciences and will be featured in the May 28th print edition.

(Philadelphia, PA) – Using "laser tweezers," researchers at the University of Pennsylvania School of Medicine have measured the strength of the bond between a single integrin molecule on the surface of a platelet and a molecule of fibrinogen, a clotting protein found in the bloodstream. An article detailing their findings was published in the May 14th online early edition of the Proceedings of the National Academy of Sciences and will be featured in the May 28th print edition.

These findings refine the current paradigm of how blood clots form. They show that changes in an integrin’s ability to bind to fibrinogen are regulated by the cell as an all-or-none phenomenon with only one functional state compatible with binding. The researchers also offer a new application for laser tweezers in studying the behavior of single molecules and the response of cells to mechanical forces.

"Laser tweezers use the force of a focused laser beam to trap and move particles. In this case, we used the tweezers to play tug-of-war with a platelet-bound integrin molecule on one side and a fibrinogen molecule mounted on a tiny latex bead on the other," said John W. Weisel, PhD, professor the Penn’s Department of Cell and Developmental Biology. "We were able to measure the force that keeps blood clots together. We can also determine the regulation of forces between individual ligand-receptor pairs and the effects of anti-clotting drugs, at the single molecule level."

Clotting is the body’s first defense against damage to blood vessels. When damaged, the cells that make up blood vessels release chemicals that activate passing platelets, causing them to adhere to the surface and aggregate. When activated, platelets change shape and expose integrin molecules – (alpha)IIb(beta)3, to be specific. The surface of a platelet contains approximately 80,000 copies of (alpha)IIb(beta)3, and each copy binds to fibrinogen, a fibrous protein that helps lash platelets together to form a clot. While clotting may stop bleeding, the formation of thrombi, or blood clots where they do not belong, may also lead to a stroke or heart attack if a clot blocks off blood vessels. So the subject of the forces involved in how clots form and dissolve are important to medical researchers. The regulation of activation of these cellular integrins must be tightly controlled to prevent thrombosis.

"Platelets are like multiple–watt lightbulbs: they can be turned on to different degrees of activation," said Weisel. "Interestingly, our findings suggest that no matter which setting you turn a platelet to, integrin binds to fibrinogen with the same affinity."

Adenosindiphosphate (ADP) and thrombin are two platelet-activating chemicals, each able to activate platelets to a different proportion, depending on their concentration. According to Weisel and his colleagues, even though more fibrinogen binds to a platelet exposed to thrombin than to ADP, it takes the same amount of force to break apart a single pair of integrin and fibrinogen molecules. It takes about 80-100 picoNewtons to separate the two molecules. By comparison, a picoNewton is about the weight of a single red blood cell and there are 500 million red cells in a drop of blood. "You can change the degree to which platelets are activated or the number of activated integrin molecules, but not the strength of the integrin bonds with fibrinogen," said Weisel.

Platelet-activating chemicals cause platelets to change shape dramatically, turning the round discs of platelets into multi-tentacled balls. This transformation allows platelets to form complex aggregates via interactions between activated integrins on these tentacles and fibrinogen in the blood. Platelet activation increases the percentage of activated integrins on the surface but the strength of integrin-fibrinogen binding is the same for each individual pair.

The trick to uncovering the strength of a single bond between proteins was the use of the laser tweezers. Laser tweezers cannot manipulate individual molecules, as such, but Penn scientists developed a new model system using tiny pedestals and beads that can be trapped and moved. To measure the bond strength, the researchers actually attached fibrinogen to microscopic plastic beads and exposed them to integrin that was either attached to pedestals or as they sat on the surface of living, reactive platelet cells.

"Laser tweezers are a remarkable tool for cell biology," said Weisel. "For the first time, we can actually measure the force of a single ligand-receptor bond, as it exists in real world, and study the cellular regulation of activation of these specific receptors."

Penn researchers involved in these findings include Rustem I. Litvinov, Henry Shuman, and Joel S. Bennett. Funding for this research was provided through grants from the National Institutes of Health.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Penn Researchers Use Laser Tweezers To Study Strength Of Ligand-Receptor Binding." ScienceDaily. ScienceDaily, 22 May 2002. <www.sciencedaily.com/releases/2002/05/020522072723.htm>.
University Of Pennsylvania Medical Center. (2002, May 22). Penn Researchers Use Laser Tweezers To Study Strength Of Ligand-Receptor Binding. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2002/05/020522072723.htm
University Of Pennsylvania Medical Center. "Penn Researchers Use Laser Tweezers To Study Strength Of Ligand-Receptor Binding." ScienceDaily. www.sciencedaily.com/releases/2002/05/020522072723.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins