Model of molecular tension. 1. CD is added to NDs loaded with MscS (gray cartoon). MscS initially adopts a closed conformation. 2. CD first sequesters the bulk lipids, which are located mostly in the ND periphery and are depleted two orders of magnitude faster than the MscS-interacting lipids. 3. CD causes irreversible delipidation as depleted lipids are permanently removed. 4. This generates gaps within the ND and a short-lived transient state during which MscS opening is initiated (5). 6. Remaining lipids, which in their majority consist of MscS-interacting lipids move to fill these gaps. 7. This lipid movement induces a membrane tension build-up, creating conditions of molecular tension, which activate MscS (open state, PDB:5AJI9).
