Native Mass Spectrometry Characterization of Intact Nanodisc Lipoprotein Complexes

We describe here the analysis of nanodisc complexes by using native mass spectrometry (MS) to characterize their molecular weight (MW) and polydispersity. Nanodiscs are nanoscale lipid bilayers that offer a platform for solubilizing membrane proteins. Unlike detergent micelles, nanodiscs are native-like lipid bilayers that are well-defined and potentially monodisperse. Their mass spectra allow peak assignment based on differences in the mass of a single lipid per complex. Resultant masses agree closely with predicted values and demonstrate conclusively the narrow dispersity of lipid molecules in the nanodisc. Fragmentation with collisionally activated dissociation (CAD) or electron capture dissociation (ECD) shows loss of a small number of lipids and eventual collapse of the nanodisc with release of the scaffold protein. These results provide a foundation for future studies utilizing nanodiscs as a platform for launching membrane proteins into the gas phase.