Peptides that form β-sheets on hydrophobic surfaces accelerate surface-induced insulin amyloidal aggregation.

Interactions between proteins and material or cellular surfaces are able to trigger protein aggregation in vitro and in vivo. The human insulin peptide segment LVEALYL is able to accelerate insulin aggregation in the presence of hydrophobic surfaces. We show that this peptide needs to be previously adsorbed on a hydrophobic surface to induce insulin aggregation. Moreover, the study of different mutant peptides proves that its sequence is less important than the secondary structure of the adsorbed peptide on the surface. Indeed, these pro-aggregative peptides act by providing stable β-sheets to incoming insulin molecules, thereby accelerating insulin adsorption locally and facilitating the conformational changes required for insulin aggregation. Conversely, a peptide known to form α-helices on hydrophobic surfaces delays insulin aggregation.