title: Mechanics of transient platelet adhesion to von Willebrand factor under flow.
abstract: A primary and critical step in platelet attachment to injured vascular endothelium is the formation of reversible tether bonds between the platelet glycoprotein receptor Ibalpha and the A1 domain of surface-bound von Willebrand factor (vWF). Due to the platelet's unique ellipsoidal shape, the force mechanics involved in its tether bond formation differs significantly from that of leukocytes and other spherical cells. We have investigated the mechanics of platelet tethering to surface-immobilized vWF-A1 under hydrodynamic shear flow. A computer algorithm was used to analyze digitized images recorded during flow-chamber experiments and track the microscale motions of platelets before, during, and after contact with the surface. An analytical two-dimensional model was developed to calculate the motion of a tethered platelet on a reactive surface in linear shear flow. Through comparison of the theoretical solution with experimental observations, we show that attachment of platelets occurs only in orientations that are predicted to result in compression along the length of the platelet and therefore on the bond being formed. These results suggest that hydrodynamic compressive forces may play an important role in initiating tether bond formation.
authors.affiliation: Department of Biomedical Engineering, University of Rochester, NY 14642, USA.
authors.forename: Nipa A
authors.initials: NA
authors.lastname: Mody
authors.forename: Oleg
authors.initials: O
authors.lastname: Lomakin
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Doggett
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Diacovo
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
mesh_terms: D000941:Antigens / Q000378:metabolism*; D001696:Biomechanical Phenomena / Q000379:methods; D001783:Blood Flow Velocity / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D003198:Computer Simulation; D017022:Flow Injection Analysis / Q000379:methods; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D040542:Mechanotransduction, Cellular / Q000502:physiology; D018715:Microscopy, Video / Q000379:methods*; D008955:Models, Cardiovascular; D010363:Pattern Recognition, Automated / Q000379:methods; D010973:Platelet Adhesiveness / Q000502:physiology*; D011485:Protein Binding; D033081:Shear Strength; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D000941:Antigens; C029417:Von Willebrand antigen; D014841:von Willebrand Factor