Dissociation of bimolecular αIIbβ3-fibrinogen complex under a constant tensile force.

ABSTRACT: The regulated ability of integrin αIIbβ3 to bind fibrinogen plays a crucial role in platelet aggregation, adhesion, and hemostasis. Employing an optical-trap-based electronic force clamp, we studied the thermodynamics and kinetics of αIIbβ3-fibrinogen bond formation and dissociation under constant unbinding forces, mimicking the forces of physiologic blood shear on a thrombus. The distribution of bond lifetimes was bimodal, indicating that the αIIbβ3-fibrinogen complex exists in two bound states with different mechanical stability. The αIIbβ3 antagonist, abciximab, inhibited binding without affecting the unbinding kinetics, whereas Mn²(+) biased the αIIbβ3-fibrinogen complex to the strong bound state with reduced off-rate. The average bond lifetimes decreased exponentially with increasing

SUBMITTER: Litvinov RI 

PROVIDER: S-EPMC3010843 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature