Cell surface glycosaminoglycans exacerbate plasma membrane perturbation induced by the islet amyloid polypeptide

Glycosaminoglycans (GAGs) are long and unbranched anionic heteropolysaccharides that have been associated with virtually all amyloid deposits. Soluble sulfated GAGs known for their propensity to promote the self-assembly of numerous amyloidogenic proteins modulate cytotoxicity. Nonetheless, although prevalent on outer leaflet eukaryotic cell plasma membrane as part proteoglycans, contributions in perturbation lipid bilayer induced by polypeptides remain unknown. Herein, we investigate roles cytotoxicity islet polypeptide (IAPP), whose deposition pancreatic islets is type II diabetes. Cellular assays using GAG-deficient cells reveal exacerbate IAPP-induced permeabilization membrane. Confocal microscopy flow cytometry analyses show IAPP sequestration at surface dependent aggregation peptide. Using giant vesicles (GPMVs) prepared from cells, direct membrane-embedded proteoglycans disassembly. In sharp contrast soluble GAGs, kinetics expose presence GPMVs does not significantly vitro formation. Overall, this study indicates increase local concentration vicinity membrane, promoting death.