Molecular tags for electron cryo-tomography

Electron cryotomography enables the direct visualisation of biological specimens without stains or fixation, revealing complex molecular landscapes at high resolution. However, identifying specific proteins within these crowded environments is challenging. Molecular tagging offers a promising solution by attaching visually distinctive markers to proteins of interest, differentiating them from the background. This review explores available tagging strategies, including gold nanoparticles, metal-binding proteins, nucleic acid nanostructures and protein-based tags. The identification and targeting strategies for each approach are discussed, highlighting their respective advantages and limitations. Future directions for advancing these tagging techniques to expand their applicability to broader research questions are also considered.