Fig. 6.

Predictions for LCAMP behavior within membranes based on the lipid–peptide topological interactions and their effects on the terms of Eq. 1 (γ, pore rim line tension; σ_G, membrane tension; and E_L, lipid–peptide interaction energy). The lipid topology of the membrane systems is indicated by block shapes, with lipids having a clustering mechanism given as a red outline. Within A, m2a generates high γ values (red) but low σ_G and E_L (green) through clustering with conical lipids along its helical face. Pore mechanism is suppressed via inefficient leaflet fold packing, while carpet mechanism is suppressed by nullification of the peptides’ positive curvature. m2a will, therefore, react via bursting. Melittin clusters the conical lipids at its C terminus and associates with the inverse conical lipids along its helical face. This generates low γ combined with high E_L at the C terminus and will respond via both pore (low γ) and carpet mechanisms (high E_L). (B) In this membrane, m2a clusters inverse conical lipids at its helical face, generating low γ and high E_L, which together with the presence of conical nonbilayer lipids allows the peptide to produce all three PIEs. Melittin generates higher γ and lower E_L and primarily reacts via bursting. (C) m2a produces low γ and high E_L through clustering with inverse conical lipids along its helical face. This will generate pore and carpet mechanisms. Melittin generates low γ and E_L and will be forced to react mainly via bursting.