'Optical tweezers' could help new blood clot treatments
'Optical tweezers' could mean new techniques for treatment of blood clots
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Friday, 05, Jun 2009 10:28
A groundbreaking technique of molecule manipulation could lead to new techniques for the treatment of blood clots.
A team, co-led by Timothy A Springer, Latham Family professor of pathology at Harvard Medical School and Children's Hospital Boston, and Wesley P Wong, Rowland Junior Fellow and a principal investigator at the Rowland Institute at Harvard, discovered a fundamental feedback mechanism that the body uses to regulate the clotting of blood.
And by using cutting-edge techniques in single-molecule manipulation, the Harvard research team uncovered new findings about how the body works to respond to injury which could have implications for the treatment of bleeding disorders.
"The human body has an incredible ability to heal from life's scrapes and bruises," explains Mr Wong in a report published in the new issue of the Science journal.
"A central aspect of this response to damage is the ability to bring bleeding to end, a process known as hemostasis. Yet regulating hemostasis is a complex balancing act."
If a person experiences too much hemostatic activity, they can suffer an excess of blood clots, resulting in a potentially deadly condition known as thrombosis.
Yet if too little hemostatic activity occurs in the body, a person may bleed to death.
The team found that to achieve the proper balance, the body relies on a largely mechanical feedback system that relies on the miniscule forces applied by the circulation system on a molecular "force sensor" known as the A2 domain of the blood clotting protein von Willebrand factor (VWF).
By manipulating single molecules of this A2 domain with so-called 'optical tweezers' developed in Mr Wong's lab, the researchers found that the A2 domain acts as a highly sensitive force sensor, responding to very weak tensile forces by unfolding, and losing much of its complex three-dimensional organization.
This unfolding event allows the cutting of the molecule by an enzyme known as ADAMTS13.
"In the body, these cutting events decrease hemostatic potential and also enable blood clots to be trimmed in size," Mr Wong added.
"The system is so finely tuned that the A2 shear sensor is able to regulate the size of VWF within the blood stream, maintaining the optimal size for responding properly to traumas."
Through enhancing the understanding of how the body is able to regulate the formation of blood clots, the findings could potentially lead to new avenues for treatment and diagnosis.