Biomechanics of haemostasis and thrombosis in health and disease: from the macro- to molecular scale

Authors

  • Reginald Tran,

    Corresponding author
    1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    2. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
    • 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, Georgia, USA
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  • David R. Myers,

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Jordan Ciciliano,

    1. 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, Georgia, USA
    2. Parker H. Petit Institute of Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Elaissa L. Trybus Hardy,

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Yumiko Sakurai,

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Byungwook Ahn,

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Yongzhi Qiu,

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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  • Robert G. Mannino,

    1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
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  • Meredith E. Fay,

    1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
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  • Wilbur A. Lam

    1. 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, Georgia, USA
    2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
    3. Parker H. Petit Institute of Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
    4. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA
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Correspondence to: Wilbur A. LAM, M.D., Ph.D.,

Emory University School of Medicine, Department of Pediatrics, 2015 Uppergate Dr. NE, ECC - 4th Floor, Rm. 412, Atlanta, GA 30322, USA.

Tel.: (404) 727-7473

Fax: (404) 727-9873

E-mail: wilbur.lam@emory.edu

Abstract

Although the processes of haemostasis and thrombosis have been studied extensively in the past several decades, much of the effort has been spent characterizing the biological and biochemical aspects of clotting. More recently, researchers have discovered that the function and physiology of blood cells and plasma proteins relevant in haematologic processes are mechanically, as well as biologically, regulated. This is not entirely surprising considering the extremely dynamic fluidic environment that these blood components exist in. Other cells in the body such as fibroblasts and endothelial cells have been found to biologically respond to their physical and mechanical environments, affecting aspects of cellular physiology as diverse as cytoskeletal architecture to gene expression to alterations of vital signalling pathways. In the circulation, blood cells and plasma proteins are constantly exposed to forces while they, in turn, also exert forces to regulate clot formation. These mechanical factors lead to biochemical and biomechanical changes on the macro- to molecular scale. Likewise, biochemical and biomechanical alterations in the microenvironment can ultimately impact the mechanical regulation of clot formation. The ways in which these factors all balance each other can be the difference between haemostasis and thrombosis. Here, we review how the biomechanics of blood cells intimately interact with the cellular and molecular biology to regulate haemostasis and thrombosis in the context of health and disease from the macro- to molecular scale. We will also show how these biomechanical forces in the context of haemostasis and thrombosis have been replicated or measured in vitro.

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