Abstract

Cryo-Transmission Electron Microscopy (cryoTEM) is a method allowing visualization of many of the delicate structures that form by self-assembly of amphiphilic molecules in aqueous environments. The amphiphiles may be surfactants, lipids, or polymers, alone or in various mixtures. The distinctive feature of the method is that the objects are examined without staining or dehydration: This is achieved by capturing the structures in very thin aqueous films, that are subsequently vitrified at liquid nitrogen temperatures and examined using a microscope. Objects in the size range from 5 to 500 nm are well suited for the method. This includes various emulsion particles, such as liposomes, and more exotic cubosomes and hexasomes. In cryoTEM investigations perforated vesicles were found, an observation that triggered extensive studies of the nature and occurrence of such structures. As a complement to scattering methods, cryoTEM has proven its value in investigations of the size and morphology of various liposomal and vesicular systems. The microscopy studies show what type of structures that are present in the sample: uni- or multilamellar vesicles, open structures or closed defect-free vesicles, whether the form is spherical, tubular, or oblate, and so on. The scattering methods give good measures of size and polydispersity for defined systems.

Three main themes are presented here. (a) Morphology of cubosomes and other emulsion particles from dispersed liquid-crystalline phases. (b) Perforated bilayers, their structure, nature, occurrence, and formation. (c) Spontaneous catanionic vesicles and their relationship to vesicles of zwitterionic lipids plus ionic surfactants.