Resolving the missing link between single platelet force and clot contractile force
Yueyi Sun,
Oluwamayokun Oshinowo,
David R. Myers,
Wilbur A. Lam,
Alexander Alexeev
Affiliations
Yueyi Sun
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30332-0405, USA
Oluwamayokun Oshinowo
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332, USA
David R. Myers
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332, USA
Wilbur A. Lam
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332, USA
Alexander Alexeev
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30332-0405, USA; Corresponding author
Summary: Blood clot contraction plays an important role in wound healing and hemostasis. Although clot contraction is known to be driven by platelets, how single platelet forces relate to the forces generated by macroscopic clots remains largely unknown. Using our microfabricated high-throughput platelet contraction cytometer, we find that single platelets have an average force of 34 nN (n=10 healthy individuals). However, multiple bulk clot experiments predict a mean single platelet force lower than 0.5 nN. To resolve this discrepancy, we use a mesoscale computational model to probe the mechanism by which individual platelets induce forces in macroscopic clots. Our experimentally informed model shows that the number of platelets in the clot cross-section defines the net clot force. We provide a relationship between single platelet force and the clot force that is useful for better understanding of blood disorders associated with bleeding and thrombosis, and facilitates the development of platelet-based and platelet-mimetic biomaterials.
