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Related Experiment Video

Updated: Jul 12, 2026

Visualizing Surface T-Cell Receptor Dynamics Four-Dimensionally Using Lattice Light-Sheet Microscopy
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Visualizing Surface T-Cell Receptor Dynamics Four-Dimensionally Using Lattice Light-Sheet Microscopy

Published on: January 30, 2020

Visualizing immunoreceptor forces and their effects in vivo.

Menglan Li, Jintian Lyu, Kaitao Li

    Biorxiv : the Preprint Server for Biology
    |July 10, 2026
    PubMed
    Summary

    Researchers developed a new tool to measure forces on immune receptors in living organisms. This synthetic Notch (SynNotch) system uses antibodies to detect mechanical signals, advancing our understanding of immune cell communication.

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    In Vivo Two-Color 2-Photon Imaging of Genetically-Tagged Reporter Cells in the Skin

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    Area of Science:

    • Immunology
    • Cell Biology
    • Biophysics

    Background:

    • Immunoreceptors are known to be modulated by forces, but in vivo demonstration has been challenging.
    • Technical limitations have hindered the study of mechanical forces acting on immune receptors within a living organism.

    Purpose of the Study:

    • To adapt a synthetic Notch (SynNotch) receptor system for in vivo reporting of forces on immunoreceptors.
    • To investigate the role of mechanical forces as a co-stimulus in CD40 and T cell receptor (TCR) signaling.

    Main Methods:

    • Adapted a SynNotch receptor by replacing its ligand-binding domain with a receptor-specific antibody to report forces.
    • Rewired Notch signaling to drive reporter gene expression (EGFP or luciferase).
    • Utilized complementary mechanobiology approaches and in vivo implantation in immunocompromised mice to validate the system.

    Main Results:

    • Demonstrated mechanically gated reporter activation for CD40 and TCR-targeting SynNotch cells in vitro and in vivo.
    • Verified that activation depends on forces generated by sender cells.
    • Showed that force acts as a biologically relevant co-stimulus, amplifying CD40 and TCR signaling.

    Conclusions:

    • Mechanically gated SynNotch reporters are a viable strategy for detecting receptor-associated mechanical signaling.
    • This approach is applicable across various systems, including 2D coculture, 3D organoids, and in vivo models.
    • The study establishes the biological relevance of force as a co-stimulus in immune receptor signaling.