Related Experiment Video

Updated: May 1, 2026

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
15:13

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy

Published on: July 25, 2014

10.9K

ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging

Kaibo Ma1, Xiaojie Ma2, João F Shida2

  • 1Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Cell
|April 29, 2026
PubMed

Insights

Oncoprotein dimerization dynamics were revealed using non-photobleaching nanoparticles. Oncogenic mutations in EGFR, HER2, and HER3 alter receptor interactions, impacting cancer signaling pathways.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Biophysics

Background:

  • ErbB receptor family dimerization is essential for cell signaling and activation.
  • The real-time dynamics and impact of oncogenic mutations on ErbB receptor dimerization are not fully understood.
  • Existing methods for observing receptor dynamics are limited by photobleaching and observation duration.

Purpose of the Study:

  • To investigate the real-time dimerization dynamics of Epidermal Growth Factor Receptor (EGFR), Human Epidermal growth factor Receptor 2 (HER2), and Human Epidermal growth factor Receptor 3 (HER3).
  • To elucidate the effects of oncogenic mutations on ErbB receptor dimerization.
  • To develop and apply a novel single-particle tracking technique for long-term observation of receptor interactions.

Main Methods:

  • Utilized long-term, multicolor single-particle tracking (SPT) in living cells.
  • Employed upconverting nanoparticles (UCNPs) as non-photobleaching probes for labeling EGFR, HER2, and HER3.
  • Enabled continuous observation of receptor interactions and dimerization dynamics.

Main Results:

  • Oncogenic EGFR mutations were found to promote stable, ligand-independent dimerization.
  • HER2 and HER3 exhibit constitutive homodimerization, suggesting a revised activation model.
  • HER2 mutations modestly increased homodimer stability, while HER3 mutations destabilized homodimers, potentially limiting heterodimerization.

Conclusions:

  • Established a comprehensive ErbB receptor interaction network, detailing diverse dimerization mechanisms.
  • Demonstrated that oncogenic mutations significantly alter ErbB receptor dimerization dynamics.
  • Provided critical insights into ErbB-mediated oncogenic signaling pathways and potential therapeutic targets.
Keywords:
ErbB receptor familydimerization networklong-term single-particle trackingoncogenic signalingupconverting nanoparticles

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