Dynamics of shear-induced ATP release from red blood cells

Jiandi Wan, William D. Ristenpart, Howard A. Stone

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release.

Original languageEnglish (US)
Pages (from-to)16432-16437
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number43
DOIs
StatePublished - Oct 28 2008

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Mechanotransduction
  • Microfluidic
  • RBCs

Fingerprint Dive into the research topics of 'Dynamics of shear-induced ATP release from red blood cells'. Together they form a unique fingerprint.

Cite this