How blood clots shrink
Image: Clotting platelets with filopodia [Weisel, University of Pennsylvania]
US-based researchers have unveiled stunning images of blood clots contracting, providing unprecedented detail on individual platelets and opening the door to new treatments for blood-related disorders.
This first view of the blood clot contraction mechanism, from Professor John W Weisel, Perelman School of Medicine, the University of Pennsylvania, and colleagues, reveals how specialised proteins in platelets cause clots to shrink in size.
Weisel and colleagues used confocal light microscopy to image the networks of fibrin fibers and blood platelets.
Investigations showed that contracting platelets cause fibrin fibres to bend, kink and cluster together, resulting in dramatic remodeling of the fibrin matrix.
Contracting platelets (green) cause bending, kinking, and local accumulation of fibrin fibers (red) resulting in dramatic remodeling of the fibrin matrix. [Alber Lab, UC Riverside.]
“Under normal circumstances, blood clot contraction plays an important role in preventing bleeding by making a better seal, since the cells become tightly packed as the spaces between them are eliminated,” says Weisel. “In this study, we unwrapped and quantified clot contraction in single platelets.”
Contraction in the microcosm of a clot entails successive steps by platelet filopodia attaching to fibrin fibers and pulling on them.
Contracting platelets cause fibrin fibres to bend, kink and accumulate. [Weisel, University of Pennsylvania]
“We found that activated platelets bend and shorten individual fibrin fibers with their filopodia, which undergo sequential extension and retraction, as if pulling hand-over-hand on a rope,” explains Weisel.
The researchers reckon that this mechanism of blood clot contraction represents a new mode of contractility by cells to reshape biological tissue.
Clot Contraction by Platelet-Attached Fibres. [Weisel, University of Pennsylvania]
As Weisel's colleague, Professor Mark Alber, from the College of Natural and Agricultural Sciences, University of California, Riverside, says: “Through this research, we have revealed a novel function for filopodia, which is their ability to re-arrange the fibrin matrix to cause clot shrinkage."
"These findings will aid in the design of thrombolytic therapeutics for enhanced treatment of blood disorders, including thrombosis and thromboembolism,” he adds.
Research is published in Nature Communications.