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

5 years ago

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

Stefanie Pannwitt, Ulrich Dietz, Udo Nubbemeyer, Tristan Bereau, Mischa Bonn, Veerappan Anbazhagan, Johannes Franz, Dirk Schneider, Tobias Weidner, Alexander Lehr

Nitrated fatty acids (NO2-FAs) act as anti-inflammatory signal mediators, albeit the molecular mechanisms behind NO2-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 NO2-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 NO2-FAs. Based on our results, we suggest a molecular mechanism of the NO2-FA in vivo activity: Driven by the NO2-FA-induced lipid layer reorganization, the structure and function of membrane-associated (signaling) proteins is indirectly affected. Lipid nitration occurs when reactive nitrogen species diffuse into the hydrophobic core of biomembranes and attack unsaturated lipids. Here, fluorescence measurements are combined with surface-specific sum frequency generation vibrational spectroscopy and coarse-grained computer simulations to demonstrate that nitro fatty acids alter lipid organization by accumulation at the membrane–water interface.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201702041