Beyond cultured cells: Frontiers in in situ structural biology

Structural biology is no longer confined to isolated macromolecules. Correlative light and electron microscopy workflows at cryogenic temperatures have been developed and optimised in cultured cell systems, opening the door for cellular structural biology. The next frontier is expanding these approaches to primary cells, tissues, biopsies, and patient material. The complexity of these samples means each presents unique challenges. Here, we review recent advances that enable the study of primary cells and complex samples. These examples demonstrate the diversity in available workflows and indicate that there is still no 'one solution for all'.