An integrin αIIbβ3 intermediate affinity state mediates biomechanical platelet aggregation

Yunfeng Chen, Lining Arnold Ju, Fangyuan Zhou, Jiexi Liao, Lingzhou Xue, Qian Peter Su, Dayong Jin, Yuping Yuan, Hang Lu, Shaun P. Jackson, Cheng Zhu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)760-769
Number of pages10
JournalNature Materials
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2019

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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