Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses

Commun Biol. 2020 Jun 4;3(1):281. doi: 10.1038/s42003-020-1002-5.

Abstract

Investigations into the nature of platelet functional variety and consequences for homeostasis require new methods for resolving single platelet phenotypes. Here we combine droplet microfluidics with flow cytometry for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin > TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level responses in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Donors / statistics & numerical data
  • Blood Platelets / physiology*
  • Collagen / metabolism*
  • Crotalid Venoms / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Lectins, C-Type / metabolism*
  • Male
  • Microfluidic Analytical Techniques
  • Middle Aged
  • Platelet Count
  • Single-Cell Analysis
  • Thrombin / metabolism*
  • Young Adult

Substances

  • Crotalid Venoms
  • Lectins, C-Type
  • convulxin
  • Collagen
  • Thrombin

Associated data

  • figshare/10.6084/m9.figshare.12086103.v1