Microclot array elastometry for integrated measurement of thrombus formation and clot biomechanics under fluid shear

Nat Commun. 2019 May 3;10(1):2051. doi: 10.1038/s41467-019-10067-6.

Abstract

Blood clotting at the vascular injury site is a complex process that involves platelet adhesion and clot stiffening/contraction in the milieu of fluid flow. An integrated understanding of the hemodynamics and tissue mechanics regulating this process is currently lacking due to the absence of an experimental system that can simultaneously model clot formation and measure clot mechanics under shear flow. Here we develop a microfluidic-integrated microclot-array-elastometry system (clotMAT) that recapitulates dynamic changes in clot mechanics under physiological shear. Treatments with procoagulants and platelet antagonists and studies with diseased patient plasma demonstrate the ability of the system to assay clot biomechanics associated with common antiplatelet treatments and bleeding disorders. The changes of clot mechanics under biochemical treatments and shear flow demonstrate independent yet equally strong effects of these two stimulants on clot stiffening. This microtissue force sensing system may have future research and diagnostic potential for various bleeding disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Blood Coagulation / drug effects*
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Female
  • Healthy Volunteers
  • Hemorrhage / diagnosis*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Microfluidics / methods*
  • Platelet Aggregation Inhibitors / pharmacology
  • Stress, Mechanical
  • Thrombelastography / methods*
  • Tissue Array Analysis / methods*
  • von Willebrand Disease, Type 2 / blood

Substances

  • Platelet Aggregation Inhibitors