Force history dependence of receptor-ligand dissociation
Force history dependence of receptor-ligand dissociation
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DOI：
10.1529/biophysj.104.050567
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发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
Zhu, C
中科院分区：
文献类型：
--
作者：
Marshall, BT;Sarangapani, KK;Zhu, C
介导细胞粘附的受体-配体键通常受到通过调节解离速率来调节其解离的力。解离速率控制受体-配体键的持续时间和它们承受的力。因此，人们应该能够从键寿命或解约束力测量来确定解离速率。然而，即使对于相同的相互作用，从两种类型的测量导出的解离速率的力依赖性之间也存在实质性差异，例如，从其配体解离的选择素，其在炎症和免疫监视期间介导白细胞在血管表面上的束缚和滚动。我们使用原子力显微镜在键寿命和解结合力实验中测量从P-选择素糖蛋白配体1或抗体解离的P-选择素的存活时间。通过一种新的数据分析方法，我们表明，这种差异是由于假设解离速率仅是力的函数而造成的。从强制解离数据得出的解离速率不仅取决于力，而且还取决于力的应用历史。这一发现为理解力如何调节受体-配体相互作用提供了新的范例。
Receptor-ligand bonds that mediate cell adhesion are often subjected to forces that regulate their dissociation via modulating off-rates. Off-rates control how long receptor-ligand bonds last and how much force they withstand. One should therefore be able to determine off-rates from either bond lifetime or unbinding force measurements. However, substantial discrepancies exist between the force dependence of off-rates derived from the two types of measurements even for the same interactions, e.g., selectins dissociating from their ligands, which mediate the tethering and rolling of leukocytes on vascular surfaces during inflammation and immune surveillance. We used atomic force microscopy to measure survival times of P-selectin dissociating from P-selectin glycoprotein ligand 1 or from an antibody in both bond lifetime and unbinding force experiments. By a new method of data analysis, we showed that the discrepancies resulted from the assumption that off-rates were functions of force only. The off-rates derived from forced dissociation data depended not only on force but also on the history of force application. This finding provides a new paradigm for understanding how force regulates receptor-ligand interactions.