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005     20260115203948.0
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100 1 _ |a Sachse, Carsten
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245 _ _ |a Cryogenic STEM of thick biological specimens
260 _ _ |a London [u.a.]
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520 _ _ |a A cryogenic scanning transmission electron microscopy (STEM) approach for analyzing thick biological specimens expands the reach of cryo-electron microscopy.In the past decade, structure determination and visualization of biological macromolecules by cryogenic electron microscopy (cryo-EM) has become one of the most popular tools in structural biology1. The power of cryo-EM has relied on the capabilities of transmission electron microscopy (TEM), which involves image formation in the microscope through electromagnetic lenses followed by comprehensive single-particle image processing. A few thousand well-defined particles can be sufficient to generate a resolution allowing reliable atomic model building. Despite the power of the established cryo-TEM approach, biological specimens can be too small, too heterogeneous or too thick and thus fall short of the commonly achieved resolutions. Moreover, determining biological structures at this resolution within the native cellular environment has only been possible in thin focused ion beam milled sections of approximately 100 nm thickness for very large and abundant macromolecular complexes such as the ribosome. In this issue, Yu et al.2 propose an alternative approach for imaging thick specimens that is based on cryogenic scanning transmission electron microscopy (STEM) followed by image processing, a method they call tilt-corrected bright-field STEM (tcBF-STEM).
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773 _ _ |a 10.1038/s41592-025-02818-9
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