Deformation of stable and toxic hIAPP oligomers by liposomes with distinct nanomechanical features and reduced cytotoxicity

Abstract

Human islet amyloid polypeptide (hIAPP) oligomers are transient due to rapid aggregation rate in vitro, but play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we report an easy and robust method to generate toxic hIAPP oligomers, which are stable for at least 8 hours. The toxic hIAPP oligomers are quickly transformed from α-helix to β-sheet by membrane phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, exhibiting distinct nanomechanical features from the hIAPP oligomers or pristine fibrils. DOPC liposomes significantly block the cytotoxicity induced by the hIAPP oligomers, which has the potential for new treatment.