A universal label‐free method for the spectroscopic investigation of polyhistidine‐tagged proteins is presented. A solid supported lipid bilayer (SSLB, picture) containing nitrilotriacetic‐acid‐modified lipids is attached on top of a germanium attenuated total reflection crystal by hydrophilic interactions. Any His tag‐modified protein can be immobilized and investigated by FTIR spectroscopy.

ATR‐FTIR spectroscopy monitors protein reactions and interactions of monolayers at the atomic level. On K. Gerwert, C. Kötting et al. describe a method to immobilize proteins by means of a polyhistidine‐tag and nitrilotriacetic‐acid‐modified lipids. Because polyhistidine tags are often used for protein purification, modified proteins are easy to access. This makes the method a universal technique for many soluble proteins. The setup allows the investigation of the secondary structure, orientation, reaction mechanisms and protein–ligand or protein–protein interactions.