“von Willebrand因子”与血小板表面上“糖蛋白Ib a”的结合调控血小板的交联，是血液凝固中的一个重要因素。利用将一个受体与其配体在单个分子中联系起来以测定结合和断开过程的一种新方法，Kim等人识别出一个以前没有被识别处的键行为类型。“受体-配体”键存在于两种截然不同的状态：一种是所谓的“轻力”(low force)状态，另一种是更为稳定的状态——该状态是当施加张力时出现的，使该键相对于所施加的力保持稳定。
这种“柔性键”行为——它涉及两组“滑动键”（键寿命随负载增加而缩短）而不是“逆锁键”（键寿命随所施加的力增加）之间的切换——的发现，对于了解与“von Willebrand因子”结合在一起的血小板何以能够抵抗外力、对于血流的增加何以会激发血小板栓子的形成都有意义。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature doi:10.1038/nature09295
A mechanically stabilized receptor–ligand flex-bond important in the vasculature
Jongseong Kim,Cheng-Zhong Zhang,Xiaohui Zhang& Timothy A. Springer
Haemostasis in the arteriolar circulation mediated by von Willebrand factor (VWF) binding to platelets is an example of an adhesive interaction that must withstand strong hydrodynamic forces acting on cells. VWF is a concatenated, multifunctional protein that has binding sites for platelets as well as subendothelial collagen1, 2. Binding of the A1 domain in VWF to the glycoprotein Ib α subunit (GPIbα) on the surface of platelets mediates crosslinking of platelets to one another and the formation of a platelet plug for arterioles3, 4. The importance of VWF is illustrated by its mutation in von Willebrand disease, a bleeding diathesis1. Here, we describe a novel mechanochemical specialization of the A1–GPIbα bond for force-resistance. We have developed a method that enables, for the first time, repeated measurements of the binding and unbinding of a receptor and ligand in a single molecule (ReaLiSM). We demonstrate two states of the receptor–ligand bond, that is, a flex-bond. One state is seen at low force; a second state begins to engage at 10?pN with a ~20-fold longer lifetime and greater force resistance. The lifetimes of the two states, how force exponentiates lifetime, and the kinetics of switching between the two states are all measured. For the first time, single-molecule measurements on this system are in agreement with bulk phase measurements. The results have important implications not only for how platelets bound to VWF are able to resist force to plug arterioles, but also how increased flow activates platelet plug formation.
