Dataset Information

Dissociation of bimolecular ?IIb?3-fibrinogen complex under a constant tensile force.

ABSTRACT: The regulated ability of integrin ?IIb?3 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 ?IIb?3-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 ?IIb?3-fibrinogen complex exists in two bound states with different mechanical stability. The ?IIb?3 antagonist, abciximab, inhibited binding without affecting the unbinding kinetics, whereas Mn²(+) biased the ?IIb?3-fibrinogen complex to the strong bound state with reduced off-rate. The average bond lifetimes decreased exponentially with increasing pulling force from ?5 pN to 50 pN, suggesting that in this force range the ?IIb?3-fibrinogen interactions are classical slip bonds. We found no evidence for catch bonds, which is consistent with the known lack of shear-enhanced platelet adhesion on fibrinogen-coated surfaces. Taken together, these data provide important quantitative and qualitative characteristics of ?IIb?3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow.

SUBMITTER: Litvinov RI

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

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Litvinov Rustem I RI Barsegov Valeri V Schissler Andrew J AJ Fisher Andrew R AR Bennett Joel S JS Weisel John W JW Shuman Henry H

Biophysical journal 20110101 1

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 ...[more]

PMID: 21190668

Similar Datasets

Project description:Viscoelasticity is a fundamental property of virtually all biological materials, and proteinaceous, fibrous materials that constitute the extracellular matrix (ECM) are no exception. Viscoelasticity may be particularly important in the ECM since cells can apply mechanical stress resulting from cell contractility over very long periods of time. However, measurements of ECM fiber response to long-term constant force loading are scarce, despite the increasing recognition that mechanical strain regulates the biological function of some ECM fibers. We developed a dual micropipette system that applies constant force to single fibers for up to 8?h. We utilized this system to study the time dependent response of fibronectin (Fn) fibers to constant force, as Fn fibers exhibit tremendous extensibility before mechanical failure as well as strain dependent alterations in biological properties. These data demonstrate the Fn fibers continue to stretch under constant force loading for at least 8?h and that this long-term creep results in plastic deformation of Fn fibers, in contrast to elastic deformation of Fn fibers under short-term, but fast loading rate extension. These data demonstrate that physiologically-relevant loading may impart mechanical features to Fn fibers by switching them into an extended state that may have altered biological functions. STATEMENT OF SIGNIFICANCE: Measurements of extracellular matrix (ECM) fiber response to constant force loading are scarce, so we developed a novel technique for applying constant force to single ECM fibers. We used this technique to measure constant force creep of fibronectin fibers since these fibers have been shown to be mechanotransducers whose functions can be altered by mechanical strain. We found that fibronectin fibers creep under constant force loading for the duration of the experiment and that this creep behavior resembles a power law. Furthermore, we found that constant force creep results in plastic deformation of the fibers, which suggests that the mechanobiological switching of fibronectin can only occur once after long-term loading.

Dataset Information

Dissociation of bimolecular ?IIb?3-fibrinogen complex under a constant tensile force.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets