Cryo transmission electron microscopy of liposomes and related structures

Cryo-transmission electron microscopy, c-TEM, has during the last 10 years contributed significantly to the understanding of the numerous, and often complex, structures formed by amphiphilic molecules in dilute aqueous solutions. In particular, the method has evolved as an important tool for the investigation of liposomes. In this review, we discuss and show examples of how the technique has been utilised to gain new information on the form and structure of liposomes, as well as on the morphological changes taking place upon encapsulation of drugs or interactions with surfactants, DNA and other polyelectrolytes. Several examples where c-TEM has been successfully employed to visualise related amphiphilic structures, such as thread-like micelles and particles of reversed phases, are also presented. In addition, we discuss recent developments concerning sample preparation and interpretation of images, as well as possible artefacts and their origin.