Heterogeneous Amyloid β-Sheet Polymorphs Identified on Hydrogen Bond Promoting Surfaces Using 2D SFG Spectroscopy

Area of Science:

• Biophysics
• Spectroscopy
• Materials Science

Background:

• Amyloid formation is linked to diseases and involves peptide self-assembly.
• The pentapeptide FGAIL, from human islet amyloid polypeptide (hIAPP), is highly amyloidogenic.
• Understanding peptide-surface interactions is crucial for controlling amyloid structure.

Purpose of the Study:

• To investigate the structural impact of hydrogen-bond promoting surfaces on the amyloidogenic pentapeptide FGAIL using 2D SFG spectroscopy.
• To differentiate between peptide structures formed on bare gold versus a mercaptobenzoic acid (MBA) monolayer.
• To elucidate the role of surface chemistry in directing amyloid polymorph formation.

Main Methods:

• Utilizing two-dimensional sum-frequency generation (2D SFG) spectroscopy to probe molecular structures.
• Studying FGAIL peptides on a pure gold surface and on a gold surface coated with a mercaptobenzoic acid (MBA) self-assembled monolayer.
• Employing computational simulations to interpret experimental spectroscopic data.

Main Results:

• FGAIL forms disordered structures on a pure gold surface.
• On an MBA-coated surface, FGAIL forms ordered beta-sheet structures, with evidence of close contact with surface carboxylic acid groups.
• Chemically ligated FGAIL peptides on the MBA monolayer exhibit simpler beta-sheet spectra, indicating a more defined structure.
• Simulations confirm that the MBA surface promotes both parallel and antiparallel beta-sheet formation with varied orientations, while ligation favors parallel sheets in a single orientation.

Conclusions:

• Hydrogen-bond promoting surfaces, like MBA, act as catalysts for heterogeneous amyloid beta-sheet polymorph formation.
• Surface interactions can either promote diverse aggregation (concentration effect) or direct specific fiber growth (ligation effect).
• The distribution of amyloid polymorphs reflects the aggregation mechanism: heterogeneous for nonselective aggregation, narrow for specific interactions.