Compression force sensing regulates integrin αiIbβ3 adhesive function on diabetic platelets

Lining Ju, James D. McFadyen, Saheb Al-Daher, Imala Alwis, Yunfeng Chen, Lotte L. Tønnesen, Sophie Maiocchi, Brianna Coulter, Anna C. Calkin, Eric I. Felner, Neale Cohen, Yuping Yuan, Simone M. Schoenwaelder, Mark E. Cooper, Cheng Zhu, Shaun P. Jackson

Research output: Contribution to journalArticlepeer-review


Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion. Analysis of discoid platelet aggregation in the mesenteric circulation of mice confirmed that diabetes leads to a marked enhancement in the formation and stability of discoid platelet aggregates, via a mechanism that is not inhibited by therapeutic doses of aspirin and clopidogrel, but is eliminated by PI 3-kinase inhibition. These studies demonstrate the existence of a compression force sensing mechanism linked to αIIbβ3 adhesive function that leads to a distinct prothrombotic phenotype in diabetes.

Original languageEnglish (US)
Article number1087
JournalNature communications
Issue number1
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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