Correlative Light‐ and Liquid‐Phase Scanning Transmission Electron Microscopy for Studies of Protein Function in Whole Cells

Abstract

Liquid‐phase scanning transmission electron microscopy (liquid STEM) is a new analytical method for studying protein function within the intact plasma membranes of cells in their native liquid environment. The resolution of liquid STEM allows macromolecular complexes in whole cells in liquid to be studied at the level of individual subunits. This chapter provides two examples of research showing the potential of this new technique for cell biology. The concept of liquid STEM presents a paradigm shift in the information that is obtained in biological electron microscopy. Instead of imaging the cellular ultrastructure in thin solid samples, the focus is shifted toward localizing protein labels in whole cells. Once one realizes how simple it is to study cells directly in liquid with correlative light and electron microscopy, and recognizes the need to study proteins in intact cells and examine larger numbers of cells, the value of this novel technology becomes clear.