High-resolution nuclear cell biology by cryo-electron tomography

The nucleus is a structurally diverse and dynamic organelle that anchors chromatin and orchestrates a large number of essential processes, including transcription, replication, ribosome biogenesis, and nucleocytoplasmic transport. Understanding how nuclear macromolecular assemblies are organized and coordinate these processes requires high-resolution imaging methods, capable of achieving sub-molecular resolution while preserving native cellular structures. Cryo-electron tomography (cryo-ET) now provides unprecedented three-dimensional views of nuclear architecture in situ, up to sub-nanometer resolution. In this review, we discuss how cryo-ET has reshaped our understanding of nuclear biology including chromatin organization, nuclear pore complex (NPC) architecture and dynamics, and chromatin–lamina interactions. We highlight how these insights have resolved long-standing debates in biology, linked nuclear structure to function, and set the stage for future developments that will bridge molecular and cellular scales.