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 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.