An integrin αIIbβ3 intermediate affinity state mediates biomechanical platelet aggregation

Nat Mater. 2019 Jul;18(7):760-769. doi: 10.1038/s41563-019-0323-6. Epub 2019 Mar 25.


Integrins are membrane receptors that mediate cell adhesion and mechanosensing. The structure-function relationship of integrins remains incompletely understood, despite the extensive studies carried out because of its importance to basic cell biology and translational medicine. Using a fluorescence dual biomembrane force probe, microfluidics and cone-and-plate rheometry, we applied precisely controlled mechanical stimulations to platelets and identified an intermediate state of integrin αIIbβ3 that is characterized by an ectodomain conformation, ligand affinity and bond lifetimes that are all intermediate between the well-known inactive and active states. This intermediate state is induced by ligand engagement of glycoprotein (GP) Ibα via a mechanosignalling pathway and potentiates the outside-in mechanosignalling of αIIbβ3 for further transition to the active state during integrin mechanical affinity maturation. Our work reveals distinct αIIbβ3 state transitions in response to biomechanical and biochemical stimuli, and identifies a role for the αIIbβ3 intermediate state in promoting biomechanical platelet aggregation.

Publication types

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

MeSH terms

  • Biomechanical Phenomena
  • Humans
  • Ligands
  • Mechanical Phenomena*
  • Platelet Aggregation*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Signal Transduction


  • Ligands
  • Platelet Glycoprotein GPIIb-IIIa Complex