Séminaire Junior du 23 Janvier 2018
Cette nouvelle année 2018 commence avec un séminaire original animé par Cédric Bouzigues (maître de conférences à l’Ecole Polytechnique de Paris-Saclay) ce mardi 23 janvier 2018 à 10h00, qui portera sur le thème des mécanismes de programmation et de contrôle en nanobiologie. L’exposé se fera en français.
Titre de l’exposé/Title : Mechanisms of Quantitative Cell Signaling Spatio-temporal Organization Revealed by Nanoimaging.
In many biological functions, the knowledge of the involved proteins is often insufficient to quantitatively predict the cell response. This is particularly true in processes, in which the physiological response results from the complex interplay of several pathways. The amount, the activation kinetics, and the spatial micro and nano-organization of signaling molecules are in these cases essential to determine the system response, which requires tight control mechanisms from the nanometric to the cell scale. A striking example is the oxidative signaling by Reactive Oxygen Species (ROS), whose production is triggered in response to a large number of different stimuli, and which both control numerous normal and pathological phenomenon. These molecules are potentially harmful for the cell, notably through their implications in cellular stress, even though they are ubiquitous secondary messengers in physiological processes. Their space and time resolved quantitative detection is thus crucial to decipher the mechanisms controlling their production.
We thus developed single lanthanide based nanoparticle imaging to quantitatively detect ROS in living cells. We indeed demonstrated that the luminescence of these particles was a relevant indicator of local oxidant concentration and we thus monitored ROS production with a ~0.5 µM accuracy and a ~1 s temporal resolution.
Based on this method, we quantitatively determined the responses to different signals, which were previously undistinguishable. We furthermore identified stimulation specific control mechanisms of ROS production kinetics in vascular cells, relying either on biochemical properties of the signaling cascade or on the nano-organization of its components. These different control modalities have significant consequences on the nature of the cell response: we notably proposed a hypothesis on the persistence of fast diffusing ROS intracellular gradient under chemotactic stimulation. Altogether, our results highlights how the spatio-temporal organization pathways, possibly at the nanoscale, have a major impact on the control of the cell response. This may furthermore have a major impact to identify critical mechanisms controlling the transition to pathological phenotypes in complex diseases such as some cancers or inflammation-related pathologies.
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