Tyler O'Neal, Staff Editor PHYSICS

Georgia Tech sheds new light on the physics of blood clotting

Research shows platelets do their job better when not in total sync with one another

Heart attacks and strokes -- the leading causes of death in human beings -- are fundamentally blood clots of the heart and brain. Better understanding how the blood-clotting process works and how to accelerate or slow down clotting, depending on the medical need, could save lives.

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

"Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury," said 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. Biochemistry is known. But how this ultimately translates into physics is an untapped area." First author Yueyi Sun inside Georgia Tech's Complex Fluids Modeling and Simulation lab, where she compares the experimental and simulated platelet-driven fibrin clot contraction process. CREDIT Alexander Alexeev, Georgia Tech

And that's a problem, argues Lam and his research colleagues, since blood clotting is ultimately 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 charge of making the initial plug. The clot that forms is called fibrin, which acts as a glue scaffold that the platelets attach to and pull against. Blood clot contraction arises when these platelets interact with the fibrin scaffold. To demonstrate the contraction, researchers embedded a 3-millimeter Jell-O mold of 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 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 said.

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 model of a contracting clot. The model incorporates fibrin fibers forming a three-dimensional network and distributed platelets that can extend filopodia, or the tentacle-like structures that extend from cells so they can attach to specific surfaces, to pull the nearby fibers.

Model Shows Platelets Dramatically Reducing Clot Volume

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 can extend filopodia that are rather short, less 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 explained. Due to the asynchronous platelet activity, the force enhancement can be as high as 70%, leading to a 90% decrease of the clot volume.

"The simulations showed that the platelets work best when they're not in total sync with each other," Lam said. "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 team asynchronous mechanical amplification, is most pronounced "when we have the right concentration of the platelets corresponding to that of healthy patients," Alexeev said.

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

The findings could open medical options for people with clotting issues, said Lam, who treats young patients with blood disorders 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 said, emphasizing 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 are bleeding from a car accident or, in the case of a heart attack, make the clotting less intense and slow 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 research also could lead to new biomaterials such as a new type of Band-Aid that could help augment 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 the platelets work together to contract the fibrin clot as they would in the body.

"When we started to include the heterogeneous activation, suddenly it gave us the correct volume contraction," she said. "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 with her research colleagues that this phenomenon might occur in other aspects of nature. For example, multiple asynchronous actuators can fold a large net more effectively to enhance packaging efficiency without the need of incorporating additional actuators.

"It theoretically could be an engineered principle," Lam said. "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 research, Sun hopes to examine more closely how a single platelet force converts or is transmitted to the clot force, and how much force is needed to hold two sides of a graph together from a thickness and width standpoint. Sun also intends to include red blood cells in their model since they account for 40% of all blood and play a role in defining the clot size.

"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 explained.

Slope stability model helps prevent landslides to protect communities, save lives

Tyler O'Neal, Staff Editor PHYSICS

Melbourne researchers able to predict landslides

A mathematical model which can predict landslides that occur unexpectantly has been developed by two University of Melbourne scientists, with colleagues from GroundProbe-Orica and the University of Florence.

Professors Antoinette Tordesillas and Robin Batterham led the work over five years to develop and test the model SSSAFE (Spatiotemporal Slope Stability Analytics for Failure Estimation), which analyses slope stability over time to predict where and when a landslide or avalanche is likely to occur.

In a study, the research team was able to predict landslides, which often cause severe disruption, economic damage, and deaths, of various sizes and speeds and in different environments.

"The key to the success of this model is that it works across a vast range of spatial or temporal scales and is informed by the physics of failure in soil and rock bodies," said Professor Tordesillas.

"It can be used at a mine, where millimeter precision measurements of the surface motion of a rock face are made every few minutes. And it can also be used in a rural area, where the only available data is a satellite radar image taken every few days to weeks."

The SSSAFE model was initially developed for mine monitoring, where landslides are a constant threat, but using publicly available satellite data, the team was able to retrospectively predict the 2017 Xinmo landslide, which buried a township in China.

"For Xinmo, the model highlighted significant movement at what became the rock avalanche source, 10 months before the disaster occurred," said Professor Tordesillas. "If we can use this model, along with freely available satellite data to recognize potential future landslide sites well before they happen, actions can be taken to protect communities, saving many lives."

With SSSAFE exploiting big data analytics, network science, and physics, Professor Tordesillas hopes her research will be used by industry and governments worldwide to help early warning systems (EWS) in mitigating landslide hazards in the face of climate change.

"Very few studies have used remote sensing data to detect precursors of slope failure. Crucially, little is known about how to interpret this data from known physics of granular failure to better understand and predict events leading to catastrophic landslides. We achieved both in SSSAFE," she said.

LSU prof develops astrophysics code that rapidly models stellar collisions

Tyler O'Neal, Staff Editor PHYSICS

A breakthrough astrophysics code, named Octo-Tiger, simulates the evolution of self-gravitating and rotating systems of arbitrary geometry using adaptive mesh refinement and a new method to parallelize the code to achieve superior speeds.

This new code to model stellar collisions is more expeditious than the established code used for numerical simulations. The research came from a unique collaboration between experimental computer scientists and astrophysicists in the Louisiana State University Department of Physics & Astronomy, the LSU Center for Computation & Technology, Indiana University Kokomo, and Macquarie University, Australia, culminating in over a year of benchmark testing and scientific simulations, supported by multiple NSF grants, including one specifically designed to break the barrier between computer science and astrophysics. 

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"Thanks to a significant effort across this collaboration, we now have a reliable computational framework to simulate stellar mergers," said Patrick Motl, professor of physics at Indiana University Kokomo. "By substantially reducing the computational time to complete a simulation, we can begin to ask new questions that could not be addressed when a single-merger simulation was precious and very time-consuming. We can explore more parameter space, examine a simulation at very high spatial resolution or for longer times after a merger, and we can extend the simulations to include more complete physical models by incorporating radiative transfer, for example."

Recently published paper investigates the code performance and precision through benchmark testing. The authors, Dominic C. Marcello, postdoctoral researcher; Sagiv Shiber, postdoctoral researcher; Juhan Frank, professor; Geoffrey C. Clayton, professor; Patrick Diehl, research scientist; and Hartmut Kaiser, research scientist, all at Louisiana State University--together with collaborators Orsola De Marco, professor at Macquarie University and Patrick M. Motl, professor at Indiana University Kokomo--compared their results to analytic solutions when known and other grid-based codes, such as the popular FLASH. Also, they computed the interaction between two white dwarfs from the early mass transfer through to the merger and compared the results with past simulations of similar systems.

"A test on Australia's fastest supercomputer, Gadi, showed that Octo-Tiger, running on a core count over 80,000, displays excellent performance for large models of merging stars," De Marco said. "With Octo-Tiger, we cannot only reduce the wait time dramatically, but our models can answer many more of the questions we care to ask."

Octo-Tiger is currently optimized to simulate the merger of well-resolved stars that can be approximated by barotropic structures, such as white dwarfs or main-sequence stars. The gravity solver conserves angular momentum to machine precision, thanks to a correction algorithm. This code uses HPX parallelization, allowing the overlap of work and communication and leading to excellent scaling properties to solve large problems in shorter time frames.

"This paper demonstrates how an asynchronous task-based runtime system can be used as a practical alternative to Message Passing Interface to support an important astrophysical problem," Diehl said.

The research outlines the current and planned areas of development aimed at tackling several physical phenomena connected to observations of transients.

"While our particular research interest is in stellar mergers and their aftermath, there are a variety of problems in computational astrophysics that Octo-Tiger can address with its basic infrastructure for self-gravitating fluids," Motl said.

The animation was prepared by Shiber, who says: "Octo-Tiger shows remarkable performance both in the accuracy of the solutions and in scaling to tens of thousands of cores. These results demonstrate Octo-Tiger as an ideal code for modeling mass transfer in binary systems and in simulating stellar mergers."