Image by Andre E.X. Brown
Thrombus
Researchers have gained “important mechanistic insights” into how von Willebrand factor (VWF) controls bleeding, according to an article published in Nature Communications.
Fluorescence imaging and microfluidic tools allowed the researchers to capture images of individual VWF molecules on camera while manipulating the molecules with life-like mechanical forces emulating natural blood flow.
This revealed that VWF undergoes a 2-step, shape-shifting transformation to activate blood clotting.
This transformation is triggered when VWF senses certain changes in blood flow that are indicative of injury.
“Under normal circumstances, VWF molecules are compact and globular in shape,” said study author Hongxia Fu, PhD, of Boston Children’s Hospital in Massachusetts.
“But we found that, when blood flow rate increases, VWF rapidly elongates, stretching out more and more in response to higher shear stress.”
However, elongating is not sufficient to activate blood clotting. It’s only when the tensile forces generated in the elongated VWF hit critical levels that the shape-shifter’s transformation becomes complete.
The tensile forces activate “sticky” sites along VWF, allowing it to adhere to circulating platelets.
Normally, the rush of blood needed to reach these critically high tensile forces can only occur at sites of injury inside blood vessels. This specificity enables VWF to sense blood loss and activate rapidly and locally, without activating elsewhere in the body.
“This experiment really represents a new platform for seeing and measuring what’s happening in the blood on a molecular level,” said study author Wesley P. Wong, PhD, of Boston Children’s Hospital.
“Through the use of novel microfluidic technologies that allow us to mimic the body’s vasculature in combination with single-molecule imaging techniques, we are finally able to capture striking images that uncover the mystery of nature’s forces at work in our bodies.”
Yan Jiang, PhD, of Boston Children’s Hospital, said the new findings could inspire smart drugs that are designed to treat obstructive clotting, like deep vein thrombosis, at only diseased areas of the body.
“When you’re putting a generic drug into the circulatory system, it’s taking effect everywhere, even in places that can cause detriment,” Dr Jiang said. “But what if we could design a smart drug that can mimic the 2-step shape-shifting of VWF and only takes effect in areas where clotting is likely to occur?”
