Characterization of Parallel β-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy

Characterization of protein secondary structures at interfaces is still challenging due to the limitations of surface-selective optical techniques. Here, we address the challenge of characterizing parallel β-sheets by combining chiral sum frequency generation (SFG) spectroscopy and computational modeling. We focus on human islet amyloid polypeptide aggregates and a de novo designed short polypeptide at lipid/water and air/glass interfaces. We find that parallel β-sheets adopt distinct orientations at various interfaces and exhibit characteristic chiroptical responses in the amide I and N–H stretch regions. Theoretical analysis indicates that the characteristic chiroptical responses provide valuable information on the symmetry, orientation, and vibrational couplings of parallel β-sheet at interfaces