Platelets and physics: How platelets "feel" and respond to their mechanical microenvironment

Blood Rev. 2015 Nov;29(6):377-86. doi: 10.1016/j.blre.2015.05.002. Epub 2015 May 8.

Abstract

During clot formation, platelets are subjected to various different signals and cues as they dynamically interact with extracellular matrix proteins such as von Willebrand factor (vWF), fibrin(ogen) and collagen. While the downstream signaling of platelet-ligand interactions is well-characterized, biophysical cues, such as hydrodynamic forces and mechanical stiffness of the underlying substrate, also mediate these interactions and affect the binding kinetics of platelets to these proteins. Recent studies have observed that, similar to nucleated cells, platelets mechanosense their microenvironment and exhibit dynamic physiologic responses to biophysical cues. This review discusses how platelet mechanosensing is affected by the hydrodynamic forces that dictate vWF-platelet interactions and fibrin polymerization and network formation. The similarities and differences in mechanosensing between platelets and nucleated cells and integrin-mediated platelet mechanosensing on both fibrin(ogen) and collagen are then reviewed. Further studies investigating how platelets interact with the mechanical microenvironment will improve our overall understanding of the hemostatic process.

Keywords: Binding kinetics; Fibrin(ogen); GPIb; Hydrodynamic forces; Integrin; Mechanosensing; Stiffness; vWF.

Publication types

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

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAMTS13 Protein
  • Blood Platelets / chemistry*
  • Blood Platelets / metabolism
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • Fibrin / genetics
  • Fibrin / metabolism
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Gene Expression Regulation
  • Humans
  • Mechanotransduction, Cellular*
  • Platelet Activation
  • Platelet Aggregation
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Platelet Glycoprotein GPIb-IX Complex / chemistry*
  • Platelet Glycoprotein GPIb-IX Complex / genetics
  • Platelet Glycoprotein GPIb-IX Complex / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • von Willebrand Factor / chemistry*
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism

Substances

  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Glycoprotein GPIb-IX Complex
  • adhesion receptor
  • von Willebrand Factor
  • Fibrin
  • Fibrinogen
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human