Mass spectrometers as cryoEM grid preparation instruments

Structure determination by single-particle cryoEM has matured into a core structural biology technique. Despite many methodological advancements, most cryoEM grids are still prepared using the plunge-freezing method developed similar to 40 years ago. Embedding samples in thin films and exposing them to the air-water interface often leads to sample damage and preferential orientation of the particles. Using native mass spectrometry to create cryoEM samples, potentially avoids these problems and allows the use of mass spectrometry sample isolation techniques during EM grid creation. We review the recent publications that have demonstrated protein complexes can be ionized, flown through the mass spectrometer, gently landed onto EM grids, imaged, and reconstructed in 3D. Although many uncertainties and challenges remain, the combination of cryoEM and MS has great potential.

Automated summary

Single-particle cryoEM has become a mature technique for structure determination in structural biology. However, the traditional plunge-freezing method used for preparing cryoEM grids still has limitations. The use of native mass spectrometry to create cryoEM samples offers a potential solution by avoiding sample damage and orientation issues. Although there are uncertainties and challenges, the combination of cryoEM and mass spectrometry shows great promise.