Figure 6.

Illustration of the membrane elastic force induced by local hydrophobic mismatch based on the mattress model (73). (A) Positive mismatch as observed in C99_ε49 and Aβ49_ζ46 substrate-bound poses is induced when the substrate protrudes through the membrane bilayer. The membrane elastic potential trying to restore the optimal membrane thickness causes a force pushing the substrate toward the PS1 active site (termed “down-pushing force”). (B) No hydrophobic mismatch was observed in the Aβ46_γ43-binding pose (elastic potential is zero or close to zero). (C) Negative mismatch observed in the Aβ43_γ40 and Aβ40_γ37 substrate-bound cases is induced when the substrate tends to contract the membrane bilayer. The membrane elastic potential keeping the membrane thickness causes an “up-pulling” force on the substrate. To see this figure in color, go online.