Single-step expansion SMLM enables molecular-resolution imaging in cells and isolated proteins

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Chem Biomed Imaging. 2026 May 13;. doi: 10.1021/cbmi.6c00054
Single-step expansion SMLM enables molecular-resolution imaging in cells and isolated proteins Lavis Lab
Taban D, Jungblut M, Budiarta M, Helmerich DA, Kiesel C, Plutkis SE, Lavis LD, Krah D, Shaib AH, Doose S, Kollmannsberger P, Rizzoli SO, Beliu G, Sauer M
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Abstract

Expansion microscopy (ExM) enables nanoscale fluorescence imaging on standard microscopes, but its combination with single-molecule localization microscopy (SMLM) remains challenging due to the incompatibility of expanded hydrogels with photoswitching buffers. Here, we introduce a single-step expansion microscopy approach that enables SMLM using spontaneously blinking dyes in 6–14× expanded samples, without re-embedding or buffer exchange. Using this approach, we achieve nanometer-scale spatial resolution by resolving the organization of the nuclear pore complex and the molecular structure of recombinant homotrimeric proliferating cell nuclear antigen.

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Preprint: https://doi.org/10.64898/2026.02.23.707413

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Janelia Authors

Sarah Plutkis
Luke Lavis
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