New Cryo-EM Polishing Technique Enables Near-Atomic Resolution Imaging of Proteins in Living Cells
Researchers developed a low-energy polishing method for cryo-focused ion beam microscopy that reduces damage to cellular samples, enabling near-atomic resolution imaging of smaller protein complexes directly within cells. Previously, in situ cryo-electron microscopy (cryo-EM) could only achieve near-atomic resolution for very large complexes like ribosomes; this advance lowers the molecular weight threshold to 400 kilodaltons. The technique could accelerate structural biology research by allowing rapid visualization of how proteins change under different cellular conditions.
Researchers have developed a cryogenic low-energy polishing approach for focused ion beam (FIB) microscopy that addresses a major limitation in in situ cryo-electron microscopy: subsurface damage to thin cellular samples. The new method produces thin lamellae with significantly reduced damage across different cell types, enabling near-atomic resolution imaging of protein complexes as small as 400 kilodaltons directly within their native cellular environments. The team demonstrated the technique by resolving multiple protein complexes from the green alga Chlamydomonas reinhardtii, including photosynthetic complexes (3.4–3.3 ångströms), metabolic enzymes (3.3 ångströms), chloroplast ribosomes (4.0 ångströms), and respiratory chain complexes (3.7 ångströms). This represents a substantial improvement over previous capabilities, which were largely limited to exceptionally large complexes. The efficient workflow also enables rapid structural feedback when cellular conditions change, offering a practical pathway for multi-condition in situ structural analysis.
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- bioRxivCenter
Low-Energy Polishing Facilitates Breaking the Resolution Barrier of In Situ Cryo-EM
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