The Effects of Lipid Membranes, Crowding and Osmolytes on the Aggregation, and Fibrillation Propensity of Human IAPP

Figure 4

Time evolution of the secondary structural change of hIAPP aggregation by studying the amide-I′ bands at 25°C after injection into the ATR-FTIR cell. (a, b) 10 μM hIAPP in the presence of a neutral (zwitterionic) DOPC bilayer. (c, d) 10 μM hIAPP in the presence of a phospholipid bilayer consisting of DOPC/DOPG (7 : 3, w/w). In (a) and (c), primary ATR-FTIR spectra are shown. In (b) and (d), intensity normalized spectra are depicted. A structural transition from partially α-helical and disordered conformations to the formation of intermolecular β-sheet occurs only in the presence of anionic lipid bilayers. (e) Schematics of the ATR-FTIR sample cell. hIAPP molecules adsorbing to and aggregating/fibrillating at the lipid bilayer membrane are detected, while those distant from the membrane are merely visible owing to the low penetration depth of the evanescent wave in the ATR-FTIR setup. Adapted and modified from [56] with permission from Elsevier.

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