A breakthrough in the physics of blood clotting

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First author Yueyi Sun in Georgia Tech’s complex fluid simulation and modeling lab, where she compares the process of contraction of experienced and simulated fibrin clots. Credit: Alexander Alexeev, Georgia Tech

Heart attacks and strokes (the leading causes of death in humans) are primarily blood clots from the heart and brain. Better understanding how the blood clotting process works and how speeding up or slowing down clotting, depending on medical need, could save lives.

New research from the Georgia Institute of Technology and Emory University published in the journal Biomaterials sheds new light on the mechanics and physics of blood clotting by modeling the dynamics at play during a still little-known phase of blood clotting called clot contraction.

“Blood clotting is actually a physics-based phenomenon that must occur to stop bleeding after an injury,” said Wilbur A. Lam, W. Paul Bowers, a research professor in the Department of Pediatrics. and the Department of Biomedical Engineering of Wallace H. Coulter. Tech and Emory. “Biology is known. Biochemistry is known. But how it ultimately translates into physics is an untapped area.”

And this is a problem, argue Lam and his research colleagues, as blood clotting is ultimately about “the quality of the seal that the body can make on this damaged blood vessel to stop bleeding or , when this goes wrong, how does the body accidentally produce clots in the vessels of the heart or brain? “

How blood clotting works

The workhorses to cause bleeding are platelets: small cells of 2 micrometers in the blood responsible for making the initial plug. The clot that forms is called fibrin, which acts as a scaffold of glue to which platelets attach and against which they stretch. Blood clot contraction occurs when these platelets interact with the fibrin scaffold. To demonstrate the contraction, the researchers embedded a 3-millimeter Jell-O mold from a LEGO figure with millions of platelets and fibrin to recreate a simplified version of a blood clot.

“What we don’t know is,‘ How does this work? “What’s the time for all these cells to work together, all come out at the same time?” These are the fundamental questions we’ve worked on together to answer, ”Lam said.

Lam’s lab collaborated with Georgia Tech’s complex fluid simulation and modeling group, led by Alexander Alexeev, a professor and member of the Anderer Faculty of the George W. Woodruff School of Mechanical Engineering, to create a computational model of a contracting clot. The model incorporates fibrin fibers forming a three-dimensional network and distributed platelets that can extend the phyllopods, or tentacle-like structures that extend from the cells so that they can attach to specific surfaces, to stretch nearby fibers.

A breakthrough in the physics of blood clotting

Two healing skin abrasions (cuts) thanks to blood clotting, a physics-based phenomenon that must occur to stop bleeding after an injury. Credit: Georgia Tech

The model shows platelets drastically reducing the volume of clots

When the researchers simulated a clot where a large group of platelets was activated at the same time, the tiny cells could only reach nearby fibrins because the platelets could spread filopods that are quite short, less than 6 micrometers. “But in a trauma, some platelets contract first. They reduce the clot so that the other platelets will see more fibrin nearby and effectively increase the strength of the clot,” Alexeev explained. Because of the asynchrony activity, the improvement in strength can reach 70%, which causes a decrease of 90% in the volume of the clot.

“The simulations showed that platelets work best when they are not fully synchronized with each other,” Lam said. “These platelets are actually pulling at different times and by doing so, they increase the efficiency (of the clot).”

This phenomenon, dubbed by the team as asynchronous mechanical amplification, is most pronounced “when we have the proper platelet concentration corresponding to that of healthy patients,” Alexeev said.

Research can lead to better ways to treat clotting and bleeding problems

The findings could open up medical options for people with clotting problems, said Lam, who treats young patients with blood disorders as a pediatric hematologist at the Allac Cancer and Blood Disorders Center at Children’s Healthcare. Atlanta.

“If we know why this is happening, we have a new potential route of treatment for diseases of ”he said, stressing that heart attacks and strokes occur when this biophysical process goes wrong.

Lam explained that fine-tuning the contraction process to make it faster or more robust could help patients who bleed from a car accident or, in the case of , make the clotting less intense and slow it down.

A breakthrough in the physics of blood clotting

(L to R) Researchers Wilbur Lam, Alexander Alexeev, and Yueyi Sun hope their findings will open up medical options for people with clotting problems. Credit: Reginald Tran, Georgia Tech

“Understanding the physics of this clot contraction could lead to new ways to treat bleeding problems and clotting problems.”

Alexeev added that his research could also lead to new biomaterials, such as a new type of Band-Aid that could help increase the clotting process.

Georgia Tech First Author and PhD Candidate Yueyi Sun noted the simplicity of the model and the fact that the simulations allowed the team to understand how platelets work together to contract the fibrin clot as they would in the body.

“When we started to include heterogeneous activation, it suddenly gave us the right volume contraction,” he said. “Allowing the platelets to have a certain time lag to be able to use what the previous ones did as the best starting point was very good to see. I think our model can potentially be used to provide guidelines for designing new biological materials and active synthetics “.

Sun agreed with his research colleagues that this phenomenon could occur in other aspects of nature. For example, several asynchronous actuators can fold a large network more efficiently to improve packaging efficiency without the need to incorporate additional actuators.

“Theoretically it could be a designed principle,” Lam said. “In order for a wound to shrink further, there may be no chemical reactions at the same time; different chemical reactions may occur at different times. Better efficiency and contraction are gained when half or all of the platelets are allowed. Do the job. together “.

Based on the research, Sun hopes to examine more closely how a single platelet force is converted or transmitted to the clot force and what force is needed to hold the two sides of a graph together from the point of view of thickness. and width. Sun also intends to include red blood cells in its model, as they account for 40% of all blood and play a role in defining clot size.

“If it is red the cells get too easily trapped in the clot and you are more likely to have a large one , which causes a thrombosis problem, “he explained.


Blood clot contraction video reveals how platelets naturally form discrete clots


More information:
Yueyi Sun et al, Platelet heterogeneity improves blood clot volumetric contraction: an example of asynchronous-mechanical amplification, Biomaterials (2021). DOI: 10.1016 / j.biomaterials.2021.120828

Citation: A breakthrough in blood clotting physics (2021, June 7) retrieved June 7, 2021 at https://medicalxpress.com/news/2021-06-breakthrough-physics-blood-clotting.html

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