Mechanism of blood clot elasticity revealed in high definition

Illinois graduate research assistant Eric Lee (left) and physics professor Klaus Schulten used steered molecular dynamics to model the behavior of every atom of the fibrinogen molecule as it was... Click here for more information.

Blood clots can save lives, staunching blood loss after injury, but they can also kill. Let loose in the bloodstream, a clot can cause a heart attack, stroke or pulmonary embolism.

A new study reveals in atomic detail how a blood protein that is a fundamental building block of blood clots gives them their life-enhancing, or life-endangering, properties.

The study, conducted by researchers at the University of Illinois and the Mayo College of Medicine, appears in the journal Structure.

Fibrinogen molecules form elastic fibers, the main material of blood clots. When a blood vessel is ruptured, signaling proteins in the blood convert fibrinogen into its active form, called fibrin. Fibrin molecules link together in a scaffold of fibers that seals the vesicle. Cells in the blood, such as platelets, fill the gaps.

Fibrinogen is highly elastic, able to reversibly stretch to two or three times its original length.

“Once they’re formed, blood clots have to be elastic because they have a mechanical function to withstand blood pressure,” said Klaus Schulten, holder of the Swanlund Chair in Physics at Illinois.

Understanding what gives fibrinogen its flexibility could help in the design of drugs to enhance their function, he said.

“We investigated what makes blood clots elastic,” said Eric Lee, a graduate research assistant and student in the M.D./Ph.D. program at Illinois. “How do we make them easier to break up or make them less likely to rupture"”

Bernard Lim, a cardiologist at Mayo and an expert on the science of blood clots, contacted Schulten’s group in 2006 for help with a puzzling finding. Lim had conducted a series of experiments using atomic force microscopy to measure the amount of force required to stretch individual fibrinogen molecules.