Heart attacks and strokes – the leading causes of death in humans – are basically blood clots of the heart and brain. Better understanding how the blood clotting process works and how to speed up or slow down clotting, depending on medical need, could save lives.
New research from Georgia Institute of Technology and Emory University published in journal Biomaterials sheds new light on the mechanics and physics of blood coagulation by modeling the dynamics at play during a still poorly understood phase of blood coagulation called clot contraction.
“Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after injury,” said Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Department of Engineering. biomedical Wallace H. Coulter in Georgia. Tech and Emory. “Biology is known. Biochemistry is known. But how it ultimately translates into physics is an untapped field.”
And that’s a problem, Lam and his research colleagues argue, since blood clotting is ultimately about “how well can the body seal on this damaged blood vessel to stop the bleeding, or when? goes wrong, how does the body accidentally clot in our heart vessels or in our brain? “
How blood clots work
The workhorses of stemming the bleeding are platelets – tiny 2 micron cells in the blood responsible for making the initial plug. The clot that forms is called fibrin, which acts like a glue scaffold that the platelets attach to and pull against. The contraction of the blood clot occurs when these platelets interact with the fibrin scaffold. To demonstrate the contraction, the researchers integrated a 3-millimeter mold with millions of platelets and fibrin to recreate a simplified version of a blood clot.
“What we don’t know is ‘How does it work?’ “What’s the timing for all of these cells to work together – are they all firing at the same time?” These are the fundamental questions we worked together to answer, ”Lam said.
Lam’s lab collaborated with Georgia Tech’s Complex Fluid Modeling and Simulation Group led by Alexander Alexeev, professor and Anderer faculty member at the George W. Woodruff School of Mechanical Engineering, to create a computer model of a contracting clot. The model incorporates fibrin fibers forming a three-dimensional network and distributed platelets that can extend the filopodia, or tentacle-like structures that extend from cells so that they can attach to specific surfaces, to pull the fibers neighbors.
The model shows platelets drastically reducing the clot volume
When the researchers simulated a clot where a large group of platelets were activated at the same time, the tiny cells could only reach neighboring fibrins because the platelets can extend into rather short filopodia, less than 6 microns. “But in trauma, some platelets contract first. They shrink the clot so that other platelets see more fibrin nearby, and this effectively increases the strength of the clot,” explained Alexeev. Due to the asynchronous platelet activity, the increase in strength can reach 70%, resulting in a 90% decrease in the volume of the clot.
“The simulations have shown that platelets perform best when they are not fully in sync with each other,” Lam said. “These platelets actually pull at different times and in doing so, they increase the efficiency (of the clot).”
This phenomenon, dubbed by the team asynchronous mechanical amplification, is most pronounced “when we have the right concentration of platelets corresponding to that of healthy patients,” said Alexeev.
Research could lead to better ways to treat clotting and bleeding issues
The findings could open up medical options for people with bleeding issues, said Lam, who treats young patients with blood disorders as a pediatric hematologist at the Aflac Cancer and Blood Disorders Center at Children’s Healthcare in Atlanta. .
“If we know why this is happening, then we have a whole new potential route of treatments for blood clotting diseases,” he said, noting that heart attacks and strokes occur when this process occurs. biophysics 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 a heart attack, make clotting less intense and blood loss. slow down.
“Understanding the physics of this clot contraction could potentially lead to new ways of treating bleeding and clotting problems. “
Alexeev added that their research could also lead to new biomaterials that could help increase the clotting process.
First author and Georgia Tech Ph.D. 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 including heterogeneous activation, it suddenly gave us the correct volume contraction,” she said. “Allowing the pads to have a certain delay so that we can use what previous ones have done as a better starting point was really interesting to see. I think our model can potentially be used to provide guidelines for the design of new biological and synthetic active materials. “
Sun agreed with his fellow researchers that this phenomenon could occur in other aspects of nature. For example, multiple asynchronous actuators can bend a large net more efficiently to improve packaging efficiency without the need to incorporate additional actuators.
“This could theoretically be an engineering principle,” Lam said. “For a wound to shrink further, maybe the chemical reactions don’t happen at the same time – maybe different chemical reactions happen at different times. You gain efficiency and contraction when you allow half or all of the pads do the job together. “
Building on the research, Sun hopes to take a closer look at how a single platelet force converts or is transmitted to clot strength, and what force is required to hold both sides of a graph together from the perspective of l ‘thickness and width. Sun also intends to include red blood cells in his model since they make up 40% of all blood and play a role in defining the size of the clot.
“If your red blood cells are too easily trapped in your clot, then you are more likely to have a large clot, which causes a thrombosis problem,” she explained.