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Updated: May 16, 2026
Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
Atomic force microscopy study of the effect of HER 2 antibody on EGF mediated ErbB ligand-receptor interaction
Xuejie Zhang1, Xiaoli Shi, Li Xu
1Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Abstract:
HER2, a member of the epidermal growth factor receptor (ErbB) family, is over-expressed in many cancers. Trastuzumab and Pertuzumab are two monoclonal antibodies targeting different extracellular domains of HER2 for cancer therapy. As Pertuzumab binds to the dimerization arm of HER2, it can block HER2 heterodimerization and in turn ErbB signaling. Whether Trastuzumab has the same function is unclear. In this work, we have applied living-cell single-molecule force spectroscopy (SMFS) by Atomic Force Microscopy (AFM) to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interaction. The results demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab. Trastuzumab is expected to exert a similar inhibition effect on HER2/EGFR dimerization as Pertuzumab, although it does not bind directly to the dimerization arm of HER2.
From The Clinical Editor:
Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors.
Insights
Trastuzumab and Pertuzumab cancer therapies inhibit enhanced EGF-EGFR binding caused by HER2. This study used single-molecule force spectroscopy to reveal how these antibodies affect receptor interactions in living cells.
Area of Science:
- Molecular biology
- Biophysics
- Cancer research
Background:
- HER2 overexpression is common in various cancers.
- Trastuzumab and Pertuzumab are monoclonal antibodies targeting HER2 for cancer therapy.
- Pertuzumab blocks HER2 dimerization and ErbB signaling; Trastuzumab's effect is less clear.
Purpose of the Study:
- To investigate the effect of Trastuzumab and Pertuzumab on HER2-modulated EGF-EGFR interaction using living-cell single-molecule force spectroscopy.
- To clarify the mechanism by which Trastuzumab impacts HER2/EGFR signaling.
Main Methods:
- Living-cell single-molecule force spectroscopy (SMFS) utilizing Atomic Force Microscopy (AFM).
- Characterization of EGF-EGFR binding dynamics in cells co-expressing EGFR and HER2.
- Assessment of antibody effects (Trastuzumab, Pertuzumab) on these interactions.
Main Results:
- EGF bound more stably to EGFR in cells co-expressing EGFR and HER2.
- Both Trastuzumab and Pertuzumab inhibited this enhanced EGF-EGFR binding.
- The study suggests Trastuzumab may inhibit HER2/EGFR dimerization similarly to Pertuzumab.
Conclusions:
- Trastuzumab and Pertuzumab can inhibit the HER2-mediated enhancement of EGF-EGFR binding.
- SMFS is a valuable technique for studying therapeutic antibody effects on membrane receptor interactions.
- Trastuzumab likely impacts HER2/EGFR dimerization, contributing to its therapeutic efficacy.
