Collaborative Research: Understanding the emergent collective biophysical behavior of platelets in blood clotting

Emory University, Atlanta GA

Investigators

Abstract

NON-TECHNICAL SUMMARY Blood clotting is a natural process that prevents blood loss from damaged vessels and restores normal blood circulation in the body. Upon injury, a chain of events culminates in the formation of a plug of cells and polymeric biomaterial that attaches to the wound edges. Platelets, the small disk-shaped cells in circulation, become activated and apply contractile forces to shrink the overall size of the clot and mechanically stabilize the repair to allow it to withstand forces applied by flowing blood and physical movements. Unhealthy changes to the blood clotting process are a leading cause of death and disability worldwide and are associated with a range of severe medical conditions such as hemophilia, stroke, and heart attack. This project seeks to investigate the complex dynamic behavior of platelets within blood clots using state of the art experimental and computational methods. As platelet biophysical properties, such as size, force, and activity can vary widely among species, the properties of platelets from humans, mice, dogs, cows, and chickens will be compared to pinpoint their influence on blood clotting. The results of this project will facilitate the development of new treatments and medical diagnostics to mitigate adverse effects of unhealthy clotting. In addition, the project will train graduate and undergraduate students in solving cross-disciplinary engineering and biomedical problems. The project will advance HealthReach, an education program aiming to engage in STEM learning K-12 students with chronic illnesses, who are often educationally disadvantaged due to frequent treatments, school absences, and other medially related issues. TECHNICAL SUMMARY This project seeks to investigate the fundamental biophysical behaviors and interactions of platelets within a blood clot that is an actively contracting material. During blood clot formation, contracting platelets pull on a nascent polymeric fibrin mesh, yet the mechanics and dynamics of this active process remain poorly understood, despite links to bleeding and clotting disorders. This is in part due to our limited understanding of platelet properties and function, especially their emerging cooperativity as they collectively apply forces to the clot fibrin network. This interdisciplinary project will integrate experiments and computational modeling to investigate clot contraction in different species including human, mouse, dog, cow, and chicken platelets that exhibit diverse physiological properties. The experiments will characterize platelet activity and interactions within the fibrin network. This information will be used to develop a mesoscale model of clot contraction that will take into account micromechanics and dynamics of platelets and will provide insight into the clot structural changes due to platelet activity and contraction. The project will focus on understanding the role of platelet heterogeneity, cooperation, activation patterns, and clot contraction mechanics to reveal the connection between the behavior of a single platelet, the collective platelet behavior, and the properties of bulk clots. By providing fundamental insights into the effects of platelet heterogeneity on the clot dynamics, the project will develop new strategies for designing novel bio-inspired active materials. Furthermore, the project will provide important insights into animal models used for bleeding and clotting research This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.