Figure 20.

Typical interaction model of hIAPP monomer with lipid bilayers via a three-step approaching–adsorption–insertion process. The hIAPP monomers with the disordered structures approach the cell membrane to establish initial contacts with their N-terminal residues via electrostatic interactions, then adjust their orientation parallel to membrane surfaces with hydrophobic residues facing toward hydrophobic tails of lipids, and finally tend to insert partially or fully into cell membranes. During the whole process, hIAPP monomers always involve the conformational changes from the bulk phase to the membrane surface to the membrane interior for inducing their potential membrane-disruption activity.