Regulation of the ROS response dynamics and organization to PDGF motile stimuli revealed by single nanoparticle imaging

Although reactive oxygen species (ROS) are better known for their harmful effects, more recently, H₂O₂, one of the ROS, was also found to act as a secondary messenger. However, details of spatiotemporal organization of specific signaling pathways that H₂O₂ is involved in are currently missing. Here, we use single nanoparticle imaging to measure the local H₂O₂ concentration and reveal regulation of the ROS response dynamics and organization to platelet-derived growth factor (PDGF) signaling. We demonstrate that H₂O₂ production is controlled by PDGFR kinase activity and EGFR transactivation, requires a persistent stimulation, and is regulated by membrane receptor diffusion. This temporal filtering is impaired in cancer cells, which may determine their pathological migration. H₂O₂ subcellular mapping reveals that an external PDGF gradient induces an amplification-free asymmetric H ₂O₂ concentration profile. These results support a general model for the control of signal transduction based only on membrane receptor diffusion and second messenger degradation.