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Related Experiment Video

Updated: Apr 14, 2026

Correlative Microscopy for 3D Structural Analysis of Dynamic Interactions
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Correlative stochastic optical reconstruction microscopy and electron microscopy.

Doory Kim1, Thomas J Deerinck2, Yaron M Sigal1

  • 1Howard Hughes Medical Institute, Cambridge, Massachusetts, United States of America; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America.

Plos One
|April 16, 2015
PubMed
Summary
This summary is machine-generated.

We developed protocols for correlative super-resolution microscopy and electron microscopy (EM), overcoming challenges in sample preparation for imaging biomolecules with nanoscale precision. These methods enable detailed cellular ultrastructure analysis.

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Area of Science:

  • Cell Biology
  • Microscopy Techniques
  • Biophysics

Background:

  • Correlative microscopy combines fluorescence and electron microscopy (EM) to visualize biomolecules within cellular ultrastructure.
  • Super-resolution microscopy offers nanometer-scale spatial resolution for molecular localization.
  • Integrating super-resolution fluorescence microscopy with EM is difficult due to incompatible specimen preparation requirements.

Purpose of the Study:

  • To develop compatible protocols for correlative stochastic optical reconstruction microscopy (STORM) and EM.
  • To enable high-resolution imaging of biomolecule distribution alongside cellular ultrastructure.
  • To overcome technical challenges in correlative super-resolution fluorescence and EM.

Main Methods:

  • Developed protocols for un-embedded samples, applying EM preparation after STORM imaging.
  • Optimized fluorescence preservation under EM fixation, staining, and embedding conditions for embedded samples.
  • Validated methods across diverse cellular targets.

Main Results:

  • Successfully integrated STORM with EM for correlative imaging.
  • Demonstrated feasibility for both un-embedded and embedded/sectioned samples.
  • Achieved high-resolution visualization of biomolecules within cellular context.

Conclusions:

  • Established robust protocols for correlative STORM and EM.
  • These methods advance the ability to study molecular localization and cellular ultrastructure simultaneously.
  • Facilitates detailed investigations into cellular organization and function at the nanoscale.