Related Experiment Video
Updated: Feb 3, 2026

Ultrastructural Localization of Endogenous LC3 by On-Section Correlative Light-Electron Microscopy
Published on: March 31, 2023
Nanobody immunostaining for correlated light and electron microscopy with preservation of ultrastructure
Tao Fang1, Xiaotang Lu2, Daniel Berger2
1Program of Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Insights
Researchers developed NATIVE microscopy to visualize molecular locations and tissue ultrastructure simultaneously. This new technique enables high-resolution 3D reconstruction of biological tissues, overcoming previous limitations.
Area of Science:
- Cell Biology
- Neuroscience
- Microscopy
Background:
- Tissue function relies on integrated morphological and molecular data.
- Conventional microscopy methods struggle to preserve ultrastructure when visualizing molecular details.
Purpose of the Study:
- To develop a novel correlated light and electron microscopy technique.
- To enable simultaneous visualization of molecular locations and ultrastructure in intact tissues.
Main Methods:
- NATIVE (Native-Array Transmission Imaging and Electron microscopy) approach.
- Correlated light and electron microscopy preserving tissue ultrastructure.
- High-resolution 3D reconstruction of biological samples.
Main Results:
- Preserved ultrastructure of tissue sections.
- Successfully mapped multiple molecular locations within deep tissue.
- Achieved large-scale 3D reconstruction of mouse hippocampal tissue at nanometer resolution.
Conclusions:
- NATIVE microscopy overcomes limitations of combined imaging techniques.
- Enables detailed nanoscale visualization of molecular organization in complex tissues.
- Facilitates advanced research in cell biology and neuroscience.
Abstract:
Morphological and molecular characteristics determine the function of biological tissues. Attempts to combine immunofluorescence and electron microscopy invariably compromise the quality of the ultrastructure of tissue sections. We developed NATIVE, a correlated light and electron microscopy approach that preserves ultrastructure while showing the locations of multiple molecular moieties, even deep within tissues. This technique allowed the large-scale 3D reconstruction of a volume of mouse hippocampal CA3 tissue at nanometer resolution.
Related Concept Videos
Overview of Electron Microscopy
Scanning Electron Microscopy
Fundamental Principles
Accelerated...
Transmission Electron Microscopy
Immunogold Electron Microscopy
Cryo-electron Microscopy
Correlations

