Recent Advances in Analyzing Protein and Peptide Structures at Interfaces Using Vibrational Sum-Frequency Generation

The structure of protein and peptide at interfaces plays a crucial role in various biological processes and technological advancements. Understanding these structures is critical for diagnosing diseases, drug delivery, and developing biomaterials. However, the complexity of these systems and limitations in analytical tools have hindered the in-depth exploration. Despite significant efforts in determining protein structures using advanced techniques like X-ray crystallography and cryo-electron microscopy, the understanding of surface-bound protein structures in real conditions remains relatively limited, posing a current challenge in this field. Vibrational sum frequency generation (SFG) spectroscopy has been developed as a versatile method for elucidating molecular structures of proteins across interfaces. This review is intended to introduce the basic principle of SFG spectroscopy, discuss its current advancements in phase measurement, and showcase recent examples (2021–2023) illustrating SFG’s ability in revealing the molecular structure of peptides and proteins at interfaces. This concise review aims to establish a foundation for future studies and applications exploring different types of peptides and proteins at interfaces using SFG.