Triggers for β-sheet formation at the hydrophobic-hydrophilic interface: high concentration, in-plane orientational order, and metal ion complexation.
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.
Department of Interfaces, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
Maria
M
Hoernke
Jessica A
JA
Falenski
Christian
C
Schwieger
Beate
B
Koksch
Gerald
G
Brezesinski
D000388:Air; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D003300:Copper / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D007477:Ions; D009942:Organometallic Compounds; D014867:Water; D003300:Copper; D015032:Zinc