Controlling human platelet activation with calcium-binding nanoparticles

David Cabrera, Karen Walker, Sandhya Moise, Neil D. Telling, Alan G.S. Harper

Research output: Contribution to journalArticlepeer-review

Abstract

Human platelets aggregate at sites of blood vessel damage in response to a rise in their cytosolic calcium concentration. Controlling these cytosolic calcium rises would provide a method to inhibit platelet activation and prevent the unwanted blood clots that causes heart attack and strokes. Previously we have predicted that calcium accumulation within the lumen of an infolded portion of the platelet plasma membrane called the open canalicular system (OCS) is essential for maintaining this cytosolic calcium rise. Due to its nanometer dimensions of the OCS, it has been difficult to measure or interfere with the predicted luminal calcium accumulation. Here we utilise iron oxide magnetic nanoparticles coated with the known calcium chelator, citrate, to create calcium-binding nanoparticles. These were used to assess whether an OCS calcium store plays a role in controlling the dynamics of human platelet activation and aggregation. We demonstrate that citrate-coated nanoparticles are rapidly and selectively uptaken into the OCS of activated human platelets, where they act to buffer the accumulation of calcium there. Treatment with these calcium-binding nanoparticles reduced thrombin-evoked cytosolic calcium rises, and slowed platelet aggregation and clot retraction in human platelets. In contrast, nanoparticles that cannot bind calcium have no effect. This study demonstrates that the OCS acts as a key source of calcium for maintaining cytosolic calcium rises and accelerating platelet aggregation, and that calcium-binding nanoparticles targeted to the OCS could provide an anti-platelet therapy to treat patients at risk of suffering heart attacks or strokes. [Figure not available: see fulltext.].

Original languageEnglish
JournalNano Research
Early online date11 Jul 2020
DOIs
Publication statusE-pub ahead of print - 11 Jul 2020

Keywords

  • calcium signaling
  • human platelets
  • nanochelators
  • nanoparticles
  • open canalicular system

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Controlling human platelet activation with calcium-binding nanoparticles'. Together they form a unique fingerprint.

Cite this