Native mass spectra of bacterial and viral nanoparticles. A: The native spectra of encapsulin, adenovirus dodecahedron (Dd9), adeno-associated virus serotype 1 (AAV1) and cowpea chlorotic mottle virus (CCMV) were acquired using a modified Orbitrap instrument. Even though the macromolecular complexes were larger than 2 MDa, the exceptional mass resolving power of the mass spectrometer allowed the determination of the particle masses with high accuracy. B: Native spectrum of the AAV1 capsid. The remarkable resolution of the spectra allowed Heck and colleagues to determine the stoichiometry of three different proteoforms (VP1, VP2, VP3) of the AAV1 capsid viral protein. C: Simulated spectra of AAV1 capsids showing different VP1:VP2:VP3 ratios. These spectra were reproduced with permission from Ref.130 © (2014) American Chemical Society.