Nanodiscs and mass spectrometry: Making membranes fly

Cells are surrounded by a protective lipid bilayer membrane, and membrane proteins in the bilayer control the flow of chemicals, information, and energy across this barrier. Many therapeutics target membrane proteins, and some directly target the lipid membrane itself. However, interactions within biological membranes are challenging to study due to their heterogeneity and insolubility. Mass spectrometry (MS) has become a powerful technique for studying membrane proteins, especially how membrane proteins interact with their surrounding lipid environment. Although detergent micelles are the most common membrane mimetic, nanodiscs are emerging as a promising platform for MS. Nanodiscs, nanoscale lipid bilayers encircled by two scaffold proteins, provide a controllable lipid bilayer for solubilizing membrane proteins. This Young Scientist Perspective focuses on native MS of intact nanodiscs and highlights the unique experiments enabled by making membranes fly, including studying membrane protein-lipid interactions and exploring the specificity of fragile transmembrane peptide complexes. It will also explore current challenges and future perspectives for interfacing nanodiscs with MS.