IAPP-induced leakage from liposomes. (A) Liposomes were prepared with encapsulated dye (Fluo-8 and Ca2+) and extraluminal EDTA. Representative leakage profiles at 10 μM (circles) and 20 μM (squares) IAPP are shown with solid lines representing single exponential fits. (B) Liposomes were prepared with membrane-associated Oregon Green DHPE. Representative leakage profiles are observed by addition of the fluorescence quencher, DPX, immediately (τDPX = 0 h, filled circles) or 2 d (τDPX = 48 h, unfilled circles) after addition of 8 μM IAPP to liposomes. (C) Semilog plot of average (N≥8) leakage rate constant versus protein concentration for initial (τDPX = 0 h, filled circles) and delayed leakage (τDPX = 48 h, unfilled circles). Solid line shows parameters derived from global fit of heterogeneous oligomer model (8) (see Discussion) to 50 kinetic profiles collected at equilibrium (τDPX = 48 h; see Fig. S5). (Inset) Replotting of data taken at τDPX = 0 h showing broader concentration range.