Electron Microscopic Analysis of the Plasma Membrane and Cell Surface Molecules

Electron microscopy is one of the most widely used techniques for visualizing biological structures including proteins, cells, and tissues. The resolution achieved by electron microscopy varies in different cases and largely depends on the quality of sample preparation. For thin samples such as proteins, plunge freezing is the most popular fixation method which can preserve the details of macromolecules at atomic or near-atomic resolution. But for thicker samples such as cells or tissues, high-pressure freezing is usually a better choice for achieving good preservation quality. The plasma membrane is a unique cellular structure that separates the cytoplasm with the outside environment and consists of a lipid bilayer embedded with various surface molecules. Due to its special location and components, the protocols for preserving membrane samples need to be optimized for visualizing the lipid bilayer and surface molecules. In this chapter, we will focus on the current strategies of the plasma membrane preservation, applications of transmission electron transmission (TEM) in studying plasma membrane structure and provide protocols of membrane sample preparation for TEM.