Figure 10. Conceptualization of the membrane deformation model of mechanosensation proposed in this study.

Lateral tension increases the open-state probability of MscS because membrane stretching increases the energetic cost of the deformations in the lipid bilayer that stabilize the closed conformation of the channel, which are largely eliminated when the structure opens. This rationalization of mechanosensitive gating does not presuppose that the closed state of the channel is structurally frustrated, but rather that it is highly stable, consistent with its greater compactness as well as with empirical observations. In addition, the proposed model does not assume that lateral tension must alter the mode of interaction between the protein and the neighboring lipids or that tension causes putative lipid binding sites to be vacated or eliminated. Instead, this ‘membrane deformation model’ recognizes that the inherent conformational preferences of the lipid bilayer contribute to dictating the overall energetics of the gating equilibrium and that the cost of any deformation is invariably dependent on the degree of lateral stretching, regardless of lipid composition.