Invited Talk

Oxidative stress regulates talin mechanosensing

King’s College London, Department of Physics, Strand Campus, London WC2R 2LS, GB

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Cellular mechanostransduction relies on the conversion of mechanical cues into chemical signals, which propagate from the focal adhesion hub through the cytoskeleton to ultimately reach the nucleus and switch on specific force-dependent transcriptional programmes. Whether the chemical properties of the environment -and namely oxidative stress- affect the first steps in mechanosensing remains unknown. Here we use a newly developed single molecule magnetic tweezers combined with UV-light to probe how oxidation of specific amino acids affects the mechanical folding of the R3 domain of the talin mechanosensor. Combined with mass spectrometry, we demonstrate that oxidation of a previously cryptic methionine to sulfone impairs vinculin binding. When translating the single molecule findings into the cellular context, we found a loss in talin/vinculin co-localisation at focal adhesions of NIH3T3 mouse fibroblasts when exposed to µM concentrations of H2O2 and a decrease in nuclear YAP. Our results showcase how specific oxidation post-translational modifications on protein mechanosensors can affect cellular mechanotransduction.