Mechanochemical Coupling Of Von Willebrand Factor And GPIb?

von Willebrand disease(VWD)is a common inherited bleeding disorder.Some types of VWD are caused by mutations in platelet and von Willebrand factor(VWF),which play important roles in the process of hemostasis.Studying the interaction between platelet and VWF will enrich our knowledge about VWD and improve the therapy.The subject of this work is the force-induced variation of the interaction between VWF A1 domain and its corresponding ligand platelet glycoprotein Ib?(GPIb?),which are significant in primary hemostasis.Optical tweezer was used to study the VWF A1-platlet GpIb? complex molecule,which was named receptor and ligand in a single molecule.External forces of different loading forms were applied to the chimeric molecule and parameters such as length of the molecule were measured and recorded.Depending on the loading form of external forces,the experiments can be divided into two categories,named force clamp experiments and force ramp experiments.External force was kept invariant in force clamp experiments whereas it changes periodically in force ramp experiments.Dudko-Hummer-Szabo equation and method developed by Serpe et al.were used to process the experiment data to calculate the force dependent lifetime.We found great agreement between results of the above two methods.Both results indicate a catch bond behavior in the reaction between VWF A1 domain and platelet GpIb?,which was previously observed by Zhu C.and his coworkers.We fitted the force dependent lifetime using the two state two pathway model based equation developed by Harder et al.and provided a structural interpretation to catch bond involving the transition between the two bond states.