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![[Figure 1]](raj5002fig1mag.jpg)
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Figure 1
From ex situ to in situ visualization across a continuum of resolution and scale from 1 Å to ∼1 µm. Structural and cellular biology techniques span complementary spatial scales. Techniques shown on the right (yellow), including NMR spectroscopy, X-ray crystallography, single-particle cryo-EM, hydrogen–deuterium exchange (HDX) and MicroED, represent ex situ structural biology approaches, in which purified or reconstituted samples are analyzed outside their native cellular environment. Techniques shown on the left (teal), including light microscopy, cell painting and super-resolution microscopy, represent in situ cellular biology methods that enable visualization within intact cells and tissues, preserving biological context. The blue curve highlights cryo-electron tomography (cryo-ET), which uniquely enables in situ structural analysis across length scales, from micrometres (∼1 µm) to near-atomic resolution (∼1 Å), through segmentation and correlative workflows at larger scales and subtomogram averaging (STA) at higher resolution. Together, these complementary approaches bridge molecular and cellular length scales, enabling high-resolution structural characterization of drug targets and complexes while also visualizing therapeutic mechanisms and effects within native cellular environments. Created in BioRender. Gabelli, S. (2026), https://BioRender.com/kl9m6ul. |
![[Figure 1]](raj5002fig1.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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