Towards Integrative and Multi-Scale Imaging with Recent Advances in Cryo-Electron Tomography
Year: 2026
Type: article
Abstract: Cryo-electron tomography (cryo-ET) enables the three-dimensional visualization of molecular architectures within complex biological environments in a near-native state. In recent years, major advances in sample preparation, instrumentation, data acquisition, and computational processing have considerably expanded the scope of cryo-ET. Workflows that were once low-throughput and largely restricted to a small number of thin specimens and use cases can now be applied to many different samples from isolated macromolecular assemblies to cells, organoids, or tissues. In parallel, the advent of (i) automatic procedures for cryo-focused ion beam milling used for sample thinning as well as streamlined tilt series acquisition, (ii) improved methods for high-pressure-frozen specimens including lift-out, (iii) together with increasingly integrated reconstruction and processing pipelines are all contributing to improve throughput, reproducibility, and accessibility of the technique. Emerging deep learning tools further facilitate target identification, quality control with feedback loops, tomogram reconstruction, and downstream analysis by sub-tomogram averaging. Here, we discuss recent developments on different aspects of the cryo-ET workflow that are progressively bridging molecular and cellular scales in conjunction with multi-modal imaging. We also highlight current limitations and emerging technologies that may further extend cryo-ET capabilities, particularly in combination with complementary approaches toward integrative structural cell biology.
DOI: 10.3390/ijms27219519
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7223990764