Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets

Nat Commun. 2018 Mar 14;9(1):1087. doi: 10.1038/s41467-018-03430-6.


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.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Aspirin / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Clopidogrel
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet Adhesiveness / drug effects
  • Platelet Adhesiveness / physiology
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / physiology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Thrombosis / metabolism*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology


  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Clopidogrel
  • Phosphatidylinositol 3-Kinases
  • Ticlopidine
  • Aspirin