Direct observation of catch bonds involving cell-adhesion molecules
Direct observation of catch bonds involving cell-adhesion molecules
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DOI：
10.1038/nature01605
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发表时间：
2003-05-08
期刊：
影响因子：
64.8
通讯作者：
Zhu, C
中科院分区：
文献类型：
--
作者：
Marshall, BT;Long, M;Zhu, C
粘附分子之间的键通常受到机械应力。一个突出的例子是施加于选择素-配体键的张力，其介导血管表面上流动的白细胞的束缚和滚动（1-3）。有人认为，力可以缩短键的寿命，因为力所做的功可以降低束缚态和自由态之间的能垒（4）（“滑移”），或者通过使分子变形，使它们锁定得更紧（5，6）（“捕获”）来延长键的寿命。尽管已经广泛观察到滑动粘结（7-14），但捕获粘结尚未在实验上得到证实。在这里，使用原子力显微镜和流动室的实验，我们表明，增加的力量第一次延长，然后缩短的P-选择素与P-选择素糖蛋白配体-1复合物的寿命，揭示了捕获和滑动键的行为。捕获键和滑动键之间的转换可能解释了为什么白细胞在选择素上滚动首先增加，然后随着壁剪切应力的增加而减少（，）（9，15）（16）。这种对力的双重响应提供了在可变机械应力条件下调节细胞粘附的机制。
Bonds between adhesion molecules are often mechanically stressed. A striking example is the tensile force applied to selectin-ligand bonds, which mediate the tethering and rolling of flowing leukocytes on vascular surfaces(1-3). It has been suggested that force could either shorten bond lifetimes, because work done by the force could lower the energy barrier between the bound and free states(4) ('slip'), or prolong bond lifetimes by deforming the molecules such that they lock more tightly(5,6) ('catch'). Whereas slip bonds have been widely observed(7-14), catch bonds have not been demonstrated experimentally. Here, using atomic force microscopy and flow-chamber experiments, we show that increasing force first prolonged and then shortened the lifetimes of P-selectin complexes with P-selectin glycoprotein ligand-1, revealing both catch and slip bond behaviour. Transitions between catch and slip bonds might explain why leukocyte rolling on selectins first increases and then decreases as wall shear stress increases(,)(9,15)(16). This dual response to force provides a mechanism for regulating cell adhesion under conditions of variable mechanical stress.