Effect of Terminal Modifications on the Adsorption and Assembly of hIAPP(20-29)

The assembly of peptides and proteins into nanoscale amyloid fibrils via formation of intermolecular β-sheets not only plays an important role in the development of degenerative diseases but also represents a promising approach for the synthesis of functional nanomaterials. In many biological and technological settings, peptide assembly occurs in the presence of organic and inorganic interfaces with different physicochemical properties. In an attempt to dissect the relative contributions of the different molecular interactions governing amyloid assembly at interfaces, we here present a systematic study of the effects of terminal modifications on the adsorption and assembly of the human islet amyloid polypeptide fragment hIAPP(20-29) at organic self-assembled monolayers (SAMs) presenting different functional groups (cationic, anionic, polar, or hydrophobic). Using a selection of complementary in situ and ex situ analytical techniques, we find that even this well-defined and comparatively simple model system is governed by a rather complex interplay of electrostatic interactions, hydrophobic interactions, and hydrogen bonding, resulting in a plethora of observations and dependencies, some of which are rather counterintuitive. In particular, our results demonstrate that terminal modifications can have tremendous effects on peptide adsorption and assembly dynamics, as well as aggregate morphology and molecular structure. The effects exerted by the terminal modifications can furthermore be modulated in nontrivial ways by the physicochemical properties of the SAM surface. Therefore, terminal modifications are an important factor to consider when conducting and comparing peptide adsorption and aggregation studies and may represent an additional parameter for guiding the assembly of peptide-based nanomaterials.