Imaging of Liposomes by Transmission Electron Microscopy

TEM is an important method for the characterization of size and shape of nanoparticles as it can directly visualize single particles and even their inner architecture. Imaging of metal particles in the electron microscope is quite straightforward due to their high density and stable structure, but the structure of soft material nanoparticles, such as liposomes, needs to be preserved for the electron microscope. The best method to visualize liposomes close to their native structure is cryo-electron microscopy, where thin films of suspensions are plunge frozen to create vitrified ice films that can be imaged directly in the electron microscope under liquid nitrogen temperature. Although subject to artifacts, negative staining TEM can also be a useful method to image liposomes, as it is faster and simpler than cryo-EM, and requires less advanced equipment.