Advances in cryo-electron microscopy and tomography (cryoEM/ET) allow us to visualize cellular ultrastructure at molecular resolution in a near-native state. By bridging the resolution between cell and structural biology, in situ cryoEM/ET unravels unprecedented molecular details of macromolecular complexes, as well as their spatial organization, within intact cells and organelles. Beyond structural determination, emerging image processing pipelines combine subtomogram averaging with contextual, quantitative, and multimodal analyses to reveal how molecules are coordinated in cellular space - what might be termed the "molecular sociology" of cells. Here, we review recent progress in specific cellular organelles, highlight key conceptual trends, and discuss current limitations and future perspectives for integrative in situ structural biology.
Jingwei Xu (Thu,) studied this question.