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

Figure 2

Three different, but not exclusive proposed mechanisms of membrane disruption by hIAPP and its aggregation. Upon binding of hIAPP with the membrane, formation of α-helical structure within monomeric hIAPP is favored due to its amphipathic nature. Initial irritation of the membrane integrity occurs. Self-assembly of hIAPP results in the formation of β-sheets and causes deeper membrane disruption. The further formation of oligomers leads to enhanced membrane disruption and disintegration either by forming pores within the lipid bilayers (1) or simply by extracting lipids from the membrane (2). At a later stage, the growth of fibrils (3) has also been observed to be responsible for membrane disruption.