title: Dimerization of Cell-Adhesion Molecules Can Increase Their Binding Strength.
abstract: Cell-adhesion molecules (CAMs) often exist as homodimers under physiological conditions. However, owing to steric hindrance, simultaneous binding of two ligands to the homodimers at the same location can hardly be satisfied, and the molecular mechanism underlying this natural design is still unknown. Here, we present a theoretical model to understand the rupture behavior of cell-adhesion bonds formed by multiple binding ligands with a single receptor. We found that the dissociation forces for the cell-adhesion bond could be greatly enhanced in comparison with the monomer case through a ligand rebinding and exchange mechanism. We also confirmed this prediction by measuring dimeric cRGD (cyclic Arg-Gly-Asp) unbinding from integrin (αvβ3) using atomic force microscopy-based single-molecule force spectroscopy. Our finding addresses the mechanism of increasing the binding strength of cell-adhesion bonds through dimerization at the single-molecule level, representing a key step toward the understanding of complicated cell-adhesion behaviors. Moreover, our results also highlight a wealth of opportunities to design mechanically stronger bioconjunctions for drug delivery, biolabeling, and surface modification.
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University , Nanjing 210093, China.
authors.forename: Wenmao
authors.identifier: 0000-0002-5044-588X
authors.initials: W
authors.lastname: Huang
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University , Nanjing 210093, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Qin
authors.affiliation: Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, School of Environmental Science and Engineering, Nanjing University of Information Science and Technology , Nanjing, Jiangsu 210044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University , Nanjing 210093, China.
authors.forename: Yi
authors.identifier: 0000-0003-1493-7868
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University , Nanjing 210093, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D015815:Cell Adhesion Molecules / Q000737:chemistry*; D039302:Integrin alphaVbeta3 / Q000737:chemistry*; D008024:Ligands; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D010456:Peptides, Cyclic / Q000737:chemistry*; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; D008024:Ligands; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide