Mass measurement of complex biomolecules
Mass photometry is universal in its applicability, as all molecules scatter light, irrespective of whether they are based on amino-acids, lipids, nucleic-acids, carbohydrates, or other building blocks. This means that not just molecules of simple composition, but also those comprising multiple biomolecular classes (e.g. glycoproteins, membrane proteins solubilised by detergent, protein-DNA complexes) are amenable to accurate mass measurement using mass photometry.
Differences in the molecular mass of heterogeneous biomolecules, such as lipid nanodiscs, are distinguishable and highly reproducible. Measurements using alternative techniques – size-exclusion chromatography, nuclear magnetic resonance spectroscopy, dynamic light scattering, and native mass spectrometry – return masses differing from each other by ~30% (orange lines). Mass photometry can assign accurate mass values to nanodiscs with variable protein belt components and lipid compositions. Analysis of lipid bilayer mimetics, such as nanodiscs, is a key capability for structural and functional studies of membrane proteins.
Data from Young et al, Science, 2018, 360 (6387), p423-7.