title: Single molecular dissection of the ligand binding property of epidermal growth factor receptor.
abstract: The understanding of ligand binding interactions is an important component of understanding the fundamental mechanism of receptor function. In this study, the binding abilities of EGF and TGF-α to EGFR on human bladder cancer (T24) cells were investigated by single molecular force spectroscopy (SMFS) based on atomic force microscopy (AFM). By approaching the specifically functionalized AFM tips to the T24 cell surface and subsequent retraction, specific unbinding events of the EGF/EGFR complexes and TGF-α/EGFR complexes were investigated. Further, the unbinding forces and the kinetic off rate constants that govern the bond stabilities were calculated through varying the external mechanic forces applied. Meanwhile, the distances from the energy minimum to the transition states along the separation paths of the EGF/EGFR complexes and TGF-α/EGFR complexes were deduced. This study at single-molecule level may enrich our understanding of the ligand binding properties of EGFR and provide some new information to the development of improved EGFR inhibitors. In addition, the results present new insight into the study of the energy landscape of the dissociation of ligand-EGFR system.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
authors.forename: Bailin
authors.initials: B
authors.lastname: Zhang
authors.forename: Jilin
authors.initials: J
authors.lastname: Tang
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D018625:Microscopy, Atomic Force / Q000379:methods*; D011485:Protein Binding; D013816:Thermodynamics; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D008024:Ligands; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors