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 H2O2 concentration profile. These results support a general model for the control of signal transduction based only on membrane receptor diffusion and second messenger degradation. [Display omitted] •ROS production kinetics imaged by single nanoparticle is stimulant dose independent•PDGF induces ROS production after a temporal filtering impaired in tumoral cells•EGFR transactivation is the first step of signal transduction in PDGF pathway•PDGF gradient induces a ROS asymmetric profile due to fast intracellular degradation Organization of intracellular reactive oxygen species (ROS) in time and space is required for regulating the cell response. Using nanoparticle imaging and microfluidics, Bouzigues et al. reveal mechanisms controlling ROS production induced by a PDGF, notably a ROS gradient mirroring the external concentration.