Intravascular effects of carbon nanotubes (CNTs) as a result of their various biomedical applications or environmental/occupational exposure raise serious safety concerns. CNTs potentiate arterial thrombosis in animal models;[1, 2] however, a mechanism of their prothrombotic effects has not been described. We have shown previously that different single-walled and multi-walled CNTs (MWCNTs), but not fullerene nC60, induce aggregation of blood platelets. We found that MWCNTs activate blood platelets by inducing extracellular Ca2+ influx sensitive to calcium entry inhibitors. Here we show that MWCNTs penetrate through platelet membranes causing injury of the dense tubular system (DTS). This is associated with a marked decrease of calcium in the platelet intracellular stores. Moreover, we demonstrate that MWCNTs induce capping of STIM1 molecules, co-localized with Orai1 molecules in platelets, which indicates activation of the store-operated calcium entry (SOCE). Our findings elucidate a mechanism of the CNT-induced platelet activation, which is critical in blood biocompatibility of carbon nanomaterials.
Citation: Nature Nanotechnology
Pub Type: Journals
carbon nanotubes, blood platelet aggregation, calcium store, calcium release, nanoparticle