Dimerization of Cell-Adhesion Molecules Can Increase Their Binding Strength

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• 作者：Wenmao HuangMeng Qin ; Ying Li ; Yi Cao ; Wei Wang
• 刊名：Langmuir
• 出版年：2017
• 出版时间：February 14, 2017
• 年：2017
• 卷：33
• 期：6
• 页码：1398-1404
• 全文大小：436K
• ISSN：1520-5827

文摘

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 (α_vβ₃) 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.