Membrane Properties Affect Opening Behaviors of the Bacterial Mechanosensitive Channel MscL: Molecular Dynamics Study

Mechanosensitive channel MscL is constituted of homopentamer of a subunit with two transmembrane inner (TM1) and outer (TM2) helices and its 3D structure of the closed state has been resolved. TM1s line an ion permeable pore and cross each other near cytoplasmic side, forming the most constricted part of the pore called gate. TM2s face lipids and some amino acids in TM2 act as a tension sensor. MscL is activated by sensing membrane tension and the major issue of MscL is to understand the gating mechanism driven by membrane tension. Previous studies propose that MscL embedded in thin membrane can activate with a lower threshold than that embedded in thick membrane. However, it remains unclear how MscL activation (opening of the gate) depends on membrane thickness in detail. In this study, we performed molecular dynamics (MD) simulations of MscL embedded in four types of lipid bilayer with different membrane thickness (DLPC, DMPC, DPPC and DSPC) to get insight into the dependency at an atomic level. As a result, it was shown also in our results that MscL in a thin lipid bilayer DLPC opened more widely than that embedded in a thick lipid bilayer DSPC. Furthremore, it was found that the thinner membrane tended to make the transmembrane helices of MscL tilt more largely. In order to check MscL-lipid interactions, we calculated the interaction energy between MscL and lipids and found that the interaction energy between Phe93 and lipids, located at the cytoplasmic side, was smaller as the membrane was thinner. This seems to be due to a hydrophobic mismatch between MscL and lipids, which affect the tilting of transmembrane helices followed by expanding of the gate during opening.