IMAGE: First creator Yueyi Sun inside Georgia Tech’s Complex Fluids Modeling and Simulation lab, the place she compares the experimental and simulated platelet-driven fibrin clot contraction course of.
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Credit: Alexander Alexeev, Georgia Tech

Heart assaults and strokes — the main causes of demise in human beings — are essentially blood clots of the coronary heart and mind. Better understanding how the blood-clotting course of works and speed up or decelerate clotting, relying on the medical want, may save lives.

New analysis by the Georgia Institute of Technology and Emory University printed in the journal Biomaterials sheds new gentle on the mechanics and physics of blood clotting by way of modeling the dynamics at play throughout a nonetheless poorly understood part of blood clotting referred to as clot contraction.

“Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury,” mentioned Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “The biology is known. The biochemistry is known. But how this ultimately translates into physics is an untapped area.”

And that is an issue, argues Lam and his analysis colleagues, since blood clotting is in the end about “how good of a seal can the body make on this damaged blood vessel to stop bleeding, or when this goes wrong, how does the body accidentally make clots in our heart vessels or in our brain?”

How Blood Clotting Works

The workhorses to stem bleeding are platelets — tiny 2-micrometer cells in the blood in cost of making the preliminary plug. The clot that varieties is named fibrin, which acts as a glue scaffold that the platelets connect to and pull towards. Blood clot contraction arises when these platelets work together with the fibrin scaffold. To show the contraction, researchers embedded a 3-millimeter Jell-O mould of a LEGO determine with hundreds of thousands of platelets and fibrin to recreate a simplified model of a blood clot.

“What we don’t know is, ‘How does that work?’ ‘What’s the timing of it so all these cells work together — do they all pull at the same time?’ Those are the fundamental questions that we worked together to answer,” Lam mentioned.

Lam’s lab collaborated with Georgia Tech’s Complex Fluids Modeling and Simulation group headed by Alexander Alexeev, professor and Anderer Faculty Fellow in the George W. Woodruff School of Mechanical Engineering, to create a computational mannequin of a contracting clot. The mannequin incorporates fibrin fibers forming a three-dimensional community and distributed platelets that may prolong filopodia, or the tentacle-like constructions that stretch from cells to allow them to connect to particular surfaces, to tug the close by fibers.

Model Shows Platelets Dramatically Reducing Clot Volume

When the researchers simulated a clot the place a big group of platelets was activated at the similar time, the tiny cells may solely attain close by fibrins as a result of the platelets can prolong filopodia which can be slightly quick, lower than 6 micrometers. “But in a trauma, some platelets contract first. They shrink the clot so the other platelets will see more fibrins nearby, and it effectively increases the clot force,” Alexeev defined. Due to the asynchronous platelet exercise, the power enhancement could be as excessive as 70%, resulting in a 90% lower of the clot quantity.

“The simulations showed that the platelets work best when they’re not in total sync with each other,” Lam mentioned. “These platelets are actually pulling at different times and by doing that they’re increasing the efficiency (of the clot).”

This phenomenon, dubbed by the group asynchronous mechanical amplification, is most pronounced “when we have the right concentration of the platelets corresponding to that of healthy patients,” Alexeev mentioned.

Research Could Lead to Better Ways to Treat Clotting, Bleeding Issues

The findings may open medical choices for folks with clotting points, mentioned Lam, who treats younger sufferers with blood problems as a pediatric hematologist in the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

“If we know why this happens, then we have a whole new potential avenue of treatments for diseases of blood clotting,” he mentioned, emphasizing that coronary heart assaults and strokes happen when this biophysical course of goes improper.

Lam defined that high quality tuning the contraction course of to make it quicker or extra strong may assist sufferers who’re bleeding from a automobile accident or, in the case of a coronary heart assault, make the clotting much less intense and gradual it down.

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

Alexeev added that their analysis additionally may result in new biomaterials akin to a brand new kind of Band-Aid that would assist increase the clotting course of.

First creator and Georgia Tech Ph.D. candidate Yueyi Sun famous the simplicity of the mannequin and the indisputable fact that the simulations allowed the group to grasp how the platelets work collectively to contract the fibrin clot as they’d in the physique.

“When we started to include the heterogeneous activation, suddenly it gave us the correct volume contraction,” she mentioned. “Allowing the platelets to have some time delay so one can use what the previous ones did as a better starting point was really neat to see. I think our model can potentially be used to provide guidelines for designing novel active biological and synthetic materials.”

Sun agreed along with her analysis colleagues that this phenomenon would possibly happen in different elements of nature. For instance, a number of asynchronous actuators can fold a big internet extra successfully to boost packaging effectivity with out the want of incorporating further actuators.

“It theoretically could be an engineered principle,” Lam mentioned. “For a wound to shrink more, maybe we don’t have the chemical reactions occur at the same time — maybe we have different chemical reactions occur at different times. You gain better efficiency and contraction when one allows half or all of the platelets to do the work together.”

Building on the analysis, Sun hopes to look at extra intently how a single platelet power converts or is transmitted to the clot power, and the way a lot power is required to carry two sides of a graph collectively from a thickness and width standpoint. Sun additionally intends to incorporate crimson blood cells in their mannequin since they account for 40% of all blood and play a task in defining the clot dimension.

“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 issue,” she defined.


CITATION: Y. Sun,, “Platelet heterogeneity enhances blood clot volumetric contraction: An example of asynchrono-mechanical amplification.” (Biomaterials 274, 120828, 2021)

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