title: von Willebrand factor, Jedi knight of the bloodstream.
abstract: When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned.
authors.affiliation: Program in Cellular and Molecular Medicine and Division of Hematology, Department of Medicine, Boston Children's Hospital, and Department of Biological Chemistry and Pharmacology, Harvard Medical School, Boston, MA.
authors.forename: Timothy A
authors.identifier: http://orcid.org/0000-0001-6627-2904
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D018056:Hemorheology; D006487:Hemostasis; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013927:Thrombosis / Q000097:blood; D014842:von Willebrand Diseases / Q000097:blood / Q000235:genetics; D014841:von Willebrand Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D014841:von Willebrand Factor