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

Biophys J. 2011 Jan 5;100(1):165-73. doi: 10.1016/j.bpj.2010.11.019.


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 pulling force from ∼5 pN to 50 pN, suggesting that in this force range the αIIbβ3-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 αIIbβ3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Antibodies, Monoclonal / pharmacology
  • Biomechanical Phenomena / drug effects
  • Fibrinogen / metabolism*
  • Humans
  • Immunoglobulin Fab Fragments / pharmacology
  • Kinetics
  • Models, Biological
  • Optical Tweezers
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Protein Binding / drug effects
  • Tensile Strength* / drug effects
  • Thermodynamics
  • Time Factors


  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Fibrinogen
  • Abciximab