title: Biomechanics of haemostasis and thrombosis in health and disease: from the macro- to molecular scale.
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.
authors.affiliation: 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 30322, USA.
authors.forename: Reginald
authors.initials: R
authors.lastname: Tran
authors.forename: David R
authors.initials: DR
authors.lastname: Myers
authors.forename: Jordan
authors.initials: J
authors.lastname: Ciciliano
authors.forename: Elaissa L
authors.initials: EL
authors.lastname: Trybus Hardy
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Byungwook
authors.initials: B
authors.lastname: Ahn
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Qiu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Mannino
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Fay
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Lam
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004912:Erythrocytes / Q000378:metabolism; D006262:Health; D006487:Hemostasis; D006801:Humans; D013927:Thrombosis / Q000097:blood / Q000503:physiopathology*