The aggregation of LCAMP helices within a small prepore region, indicated by the dashed white line, can potentially accumulate significant membrane packing frustration (EL) within a small region. (A) m2a helices surrounded by inverse conical lipids form high-energy lipid–peptide interactions (red shading). Together with the efficient pore leaflet fold packing of inverse conical lipids, this satisfies the conditions for pore formation (i.e., renders ER < 0). (B) m2a surrounded by conical lipids generates low EL (green shading). Conical lipids also increase γ, leaving the raft assembly unable to satisfy the conditions for pore formation.