Membrane Geometry Alters the Interaction between Islet Amyloid Polypeptide and Lipid Bilayers

Islet amyloid polypeptide (IAPP) is a small, amyloidogenic peptide associated with the pathology of Type 2 Diabetes. In vitro, the presence of anionic lipids significantly enhances the amyloidogenic behavior of IAPP. Moreover, IAPP causes leakage of synthetic lipid vesicles, as well as cell death when added exogenously to cultured mammalian cells. In order to probe the mechanism by which IAPP disrupts lipid bilayers, we have studied its interactions with two different model membranes-Nanodiscs and vesicles-using a combination of fluorescence correlation spectroscopy (FCS) and ensemble fluorescence measurements. We find that IAPP binds to these two model systems with different affinities. Our results illustrate that different membrane geometries modulate the interaction of IAPP with lipid bilayers, and therefore, may affect both amyloid formation and membrane leakage.