Investigations of EGFR configurations on tumor cell surface by high-resolution electron microscopy

Epidermal growth factor receptor (EGFR) is an important target for tumor therapy in various tumors. The current understanding of EGFR conformations on the cell surface is based on X-ray structural data, molecular dynamic simulations, and fluorescence-localization imaging. Using scanning electron mic...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-11, Vol.532 (2), p.179-184
Main Authors: Wang, Li, Li, Jintao, Zhang, Na, Zhang, Xiaofei, Xia, Yang, Chai, Binbin, Gao, Chunlang, Mao, Shengcheng, Ji, Yuan, Sheng, Wang, Han, Xiaodong
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Configuration
EGFR
ErbB Receptors - analysis
ErbB Receptors - chemistry
ErbB Receptors - metabolism
Female
Gold - chemistry
Humans
Metal Nanoparticles - chemistry
Microscopy, Electron, Scanning - methods
Microscopy, Electron, Transmission - methods
Oligomerization
Protein Multimerization
SEM
Structural model
TEM
Triple Negative Breast Neoplasms - metabolism
Triple Negative Breast Neoplasms - pathology
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Summary:Epidermal growth factor receptor (EGFR) is an important target for tumor therapy in various tumors. The current understanding of EGFR conformations on the cell surface is based on X-ray structural data, molecular dynamic simulations, and fluorescence-localization imaging. Using scanning electron microscope (SEM) and transmission electron microscope (TEM) with the resolution at sub-nanometers, we successfully recognized individual molecules of EGFRs and their assembly details on the surface of triple-negative breast cancer (TNBC) upon one-to-one labeling by Au nanoparticles. Based on our results, we have proposed the possible configurations, structural models, and conformational transitions of EGFR oligomers. Our study shows that the high-resolution electron imaging is an invaluable tool to provide direct evidence of EGFR configuration on tumor cell surfaces, and may play a pivotal role in further understanding of EGFR-associated signaling and tumor therapy. [Display omitted] •Using high resolution SEM image of 4–5 nm to recognize individual EGFR on TNBC cells .•Proposal possible conformation modeling and interaction of extracellular EGFR oligomers, e.g., trimers, tetramers, and complex polymers based on high resolution TEM images .•The outcomes of this work will improve the way new diagnostics are being designed around EGFR structure, function, and biology. .
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.07.018