title: Mechanical activation of a multimeric adhesive protein through domain conformational change.
abstract: The mechanical force-induced activation of the adhesive protein von Willebrand factor (VWF), which experiences high hydrodynamic forces, is essential in initiating platelet adhesion. The importance of the mechanical force-induced functional change is manifested in the multimeric VWF's crucial role in blood coagulation, when high fluid shear stress activates plasma VWF (PVWF) multimers to bind platelets. Here, we showed that a pathological level of high shear stress exposure of PVWF multimers results in domain conformational changes, and the subsequent shifts in the unfolding force allow us to use force as a marker to track the dynamic states of the multimeric VWF. We found that shear-activated PVWF multimers are more resistant to mechanical unfolding than nonsheared PVWF multimers, as indicated in the higher peak unfolding force. These results provide insight into the mechanism of shear-induced activation of PVWF multimers.
authors.affiliation: Department of Physics and Astronomy, Rice University, Houston, Texas 77005, USA.
authors.forename: Sithara S
authors.initials: SS
authors.lastname: Wijeratne
authors.forename: Eric
authors.initials: E
authors.lastname: Botello
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Yeh
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Angela L
authors.initials: AL
authors.lastname: Bergeron
authors.forename: Eric W
authors.initials: EW
authors.lastname: Frey
authors.forename: Jay M
authors.initials: JM
authors.lastname: Patel
authors.forename: Leticia
authors.initials: L
authors.lastname: Nolasco
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Turner
authors.forename: Joel L
authors.initials: JL
authors.lastname: Moake
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Kiang
mesh_terms: D008954:Models, Biological; D010974:Platelet Aggregation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D013816:Thermodynamics; D014841:von Willebrand Factor / Q000737:chemistry*
chemical_list: D014841:von Willebrand Factor