Mechanical and molecular activation lead to structurally analogous MscL states 1

25 The mechanosensitive channel of large conductance MscL gates in response to tension changes 26 in the membrane to allow the exchange of molecules through its pore. Native ligands that bind and 27 modulate MscL are unknown and trapping an activated state has been challenging. Disruption of 28 lipid access to tension-sensitive transmembrane pockets by modification leads to a concerted 29 structural and functional MscL response. However, it is unknown whether there is structural 30 correlation between tension mediated and molecular activation in mechanosensitive channels. 31 Here, we combine HDX mass spectrometry and ESEEM solvent accessibility measurements on 32 MscL, coupled with molecular dynamics under bilayer tension, to investigate the structural changes 33 associated with the two distinctively derived states. Membrane thinning is not sufficient to hydrate 34