Large mechanosensitive ion channel: MscL, with a subunit size of 136 aas with 2 TMSs; it catalyzes efflux of ions (slightly cation selective), osmolytes and small proteins. Residues in the putative primary gate are present in the first TMS (Levin and Blount 2004). Protein-lipid interactions are important for gating, dependent on TMS tilting (Iscla et al., 2011b).  The carboxyl-terminal cytoplasmic helices assemble into a pentameric bundle that resembles cartilage oligomeric matrix protein, and these are required for the selective formation of the pentamer (Ando et al. 2015). Lysophospholipids can increase the size of particles that can be transported (Foo et al. 2015). 500 - 700 channels are needed for 80% survival follwing a large changes in osmotic pressure, a number of channels similar to that found in wild type E. coli cells (Chure et al. 2018). its activation threshold decreases with membrane thickness; the membrane-thickness-dependent MscL opening mainly arises from structural changes in MscL to match the altered membrane thickness by stretching (Katsuta et al. 2018). MscL can provide a route for antibiotic entry into the E. coli cell, and agonists are available to facilitate their entry (Wray et al. 2020; Zhao et al. 2020). MscL has been used to design a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells (Hindley et al. 2019). Available information at the ultrastructural level on lipids tightly bound to transport proteins and the impact of altered bulk membrane lipid composition has been reviewed (Stieger et al. 2021). Competition between hydrophobic mismatch and tension may result in opening tension for MscL (Wiggins and Phillips 2004). The amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane (Bavi et al. 2016).