Triggers for β-Sheet Formation at the Hydrophobic–Hydrophilic Interface: High Concentration, In-Plane Orientational Order, and Metal Ion Complexation

Abstract

Amyloid formation plays a causative role in neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Soluble peptides form β-sheets that subsequently rearrange into fibrils and deposit as amyloid plaques. Many parameters trigger and influence the onset of the β-sheet formation. Early stages are recently discussed to be cell-toxic. Aiming at understanding various triggers such as interactions with hydrophobic-hydrophilic interfaces and metal ion complexation and their interplay, we investigated a set of model peptides at the air-water interface. We are using a general approach to a variety of diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes that are connected to amyloid formation. Surface sensitive techniques combined with film balance measurements have been used to assess the conformation of the peptides and their orientation at the air-water interface (IR reflection-absorption spectroscopy). Additionally, the structures of the peptide layers were characterized by grazing incidence X-ray diffraction and X-ray reflectivity. The peptides adsorb to the air-water interface and immediately adopt an α-helical conformation. This helical intermediate transforms into β-sheets upon further triggering. The factors that result in β-sheet formation are dependent on the peptide sequence. In general, the interface has the strongest effect on peptide conformation compared to high concentrations or metal ions. Metal ions are able to prevent aggregation in bulk but not at the interface. At the interface, metal ion complexation has only minor effects on the peptide secondary structure, influencing the in-plane structure that is formed in two dimensions. At the air-water interface, increased concentrations or a parallel arrangement of the α-helical intermediates are the most effective triggers. This study reveals the role of various triggers for β-sheet formation and their complex interplay. Our main finding is that the hydrophobic-hydrophilic interface largely governs the conformation of peptides. Therefore, the present study implies that special care is needed when interpreting data that may be affected by different amounts or types of interfaces during experimentation.

Protein/Peptide Aggregation and Amyloidosis on Biointerfaces

“…Hence, for peptide (i, i + 2), Zn 2+ could not inhibit the conformational transition from α-helix into β -sheets by stabilizing the α -helical structure through complexation. These results are consistent with those of Brezesinski et al in 2012 [78]. They concluded that the hydrophobic–hydrophilic interface largely determines the conformational transition of the absorbed peptide and mainly influences peptide aggregation, compared with metal ions or even peptide concentration.…”

Hereditary Systemic Amyloidosis Due to Asp76Asn Variant β2-Microglobulin

“…2D). Fibril formation by the variant was markedly enhanced by shaking the protein solution, a recognized promoter of β-sheet aggregation, 16 which overexposes the protein to the water-air interface, mimicking the in vivo environment at the interface between polar and nonpolar surfaces. However, under physiologic solvent conditions, the D76N variant was fully converted into fibrils with classic amyloid-like properties within 48 hours, whereas the wild-type protein did not aggregate at all (Fig.…”

Interactions of Two Fragments of the Human Antimicrobial Peptide LL-37 with Zwitterionic and Anionic Lipid Monolayers

“…To compare the orientation of the peptides, the dichroic ratio (intensity of the p-polarized light divided by the intensity of the s-polarized light) of the amide I band has been analyzed [50,59]. It is independent of the concentration or length of the peptides and allows comparisons regarding the orientation in both, inplane and out-of-plane directions.…”