All-optical Super-resolution Imaging of Molecules in Their Nanoscale Cellular Context

Jörg Bewersdorf

Jörg Bewersdorf

Super-resolution optical microscopy has become a powerful tool to study the nanoscale spatial distribution of proteins of interest in cells over the last years. Imaging these distributions in the context of other proteins or the general cellular context is, however, still challenging. I will present recent developments of our lab which facilitate access to super-resolution microscopy for a broader community: A new fluorogenic DNA-PAINT probe enables fast, high-quality, 3D whole-cell imaging without the need for optical sectioning, adding a versatile and easily accessible tool to the toolbox of single-molecule super-resolution probes [1]. Labeling proteins and other cellular components in bulk in our recently developed pan-Expansion Microscopy method provides ultrastructural context to the nanoscale organization of proteins, replacing complex correlative light/electron microscopy by an all-optical approach to imaging cells and brain tissue sections [2, 3].  

Financial Interest Disclosure: J.B. has financial interest in Bruker Corp. and Hamamatsu Photonics and is co-founder of a startup company related to Expansion Microscopy.

[1] Chung, K.K.H., et al. “Fluorogenic DNA-PAINT for faster, low-background super-resolution imaging”. Nat Methods (2022).
[2] M’Saad, O., Bewersdorf, J. “Light microscopy of proteins in their ultrastructural context”. Nat Commun 11, 3850 (2020).

[3] M’Saad, O., et al. “All-optical visualization of specific molecules in the ultrastructural context of brain tissue”. bioRxiv (2022).


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