In situ surface-enhanced Raman spectroscopy for membrane protein analysis and sensing

Membrane proteins are involved in a variety of dynamic cellular processes and exploration of the structural basis of membrane proteins is of significance for a better understanding of their functions. In situ analysis of membrane proteins and their dynamics is, however, challenging for conventional techniques. Surface-enhanced Raman spectroscopy (SERS) is powerful in protein structural characterization, allowing for sensitive, in-situ and real-time identification and dynamic monitoring under physiological conditions. In this review, the applications of SERS in probing membrane proteins are outlined, discussed and prospected. It starts with a brief introduction to membrane proteins, SERS theories and SERS-based strategies that commonly-used for membrane proteins. How to assemble phospholipid biolayers on SERS-active materials is highlighted, followed by respectively discussing about direct and indirect strategies for membrane protein sensing. SERS-based monitoring of protein-ligand interactions is finally introduced and its potential in biomedical applications is discussed in detail. The review ends with critical discussion about current challenges and limitations of this research field, and the promising perspectives in both fundamental and applied sciences.