Single Particle Analysis of Liposome Leakage Induced by Islet Amyloid Polypeptide

Abstract

Islet Amyloid Polypeptide (IAPP) is a 37-residue peptide hormone co-secreated with insulin from pancreatic β-cells. In patients suffering from type-2 diabetes mellitus (T2D), IAPP forms amyloid fibers in the pancreas, which are associated with cell death and the progression of the disease. A possible mechanism of cytotoxicity in T2D is the permeablizing of membranes by oligomeric IAPP, followed by leakage of ions or other molecules. We are examining the IAPP-induced leakage of individual liposomes through the use of single particle methods. Individual fluorescently labeled liposomes are measured post-IAPP exposure through the use of single particle burst analysis to determine the distribution of leakage states. By determining the role of individual residues, solution conditions, and lipid composition in modulating leakage insights are made into the mechanism of oligomer-mediated membrane leakage.