Nitrated Fatty Acids Modulate the Physical Properties of Model Membranes and the Structure of Transmembrane Proteins

Abstract

Abstract Nitrated fatty acids (NO 2 ‐FAs) act as anti‐inflammatory signal mediators, albeit the molecular mechanisms behind NO 2 ‐FAs’ influence on diverse metabolic and signaling pathways in inflamed tissues are essentially elusive. Here, we combine fluorescence measurements with surface‐specific sum frequency generation vibrational spectroscopy and coarse‐grained computer simulations to demonstrate that NO 2 ‐FAs alter lipid organization by accumulation at the membrane–water interface. As the function of membrane proteins strongly depends on both, protein structure as well as membrane properties, we consecutively follow the structural dynamics of an integral membrane protein in presence of NO 2 ‐FAs. Based on our results, we suggest a molecular mechanism of the NO 2 ‐FA in vivo activity: Driven by the NO 2 ‐FA‐induced lipid layer reorganization, the structure and function of membrane‐associated (signaling) proteins is indirectly affected.