Biomechanics of leukocyte rolling.
Biomechanics of leukocyte rolling.
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DOI：
10.3233/bir-2011-0579
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发表时间：
2011
期刊：
影响因子：
1.1
通讯作者：
Ley K
中科院分区：
文献类型：
--
作者：
Sundd P;Pospieszalska MK;Cheung LS;Konstantopoulos K;Ley K
白细胞在内皮细胞和其他P-选择素底物上的滚动是由P-选择素与白细胞微绒毛顶端表达的P-选择素糖蛋白配体-1结合介导的。白细胞滚动是在流体动力学剪切力存在下选择素-配体键的快速但平衡的形成和解离的结果。作用在键上的流体动力可以增加（捕获键）或减少（滑动键）它们的寿命。力依赖的“捕捉-滑移”键动力学解释使用键解离的“双路径模型”。“滑动-再结合”和“变构”机制都将“捕获-滑动”键行为归因于力诱导的选择素的凝集素-EGF结构域铰链中的构象变化。低于阈值剪切应力，选择蛋白不能介导滚动。这种“剪切阈值”现象是剪切增强系留和捕获结合增强滚动的结果。定量动态足迹显微镜显示，在小静脉剪切应力（> 0.6 Pa）下滚动的白细胞发生细胞变形（大足迹）并形成长系链。作用在滚动细胞上的流体动力剪切力和扭矩被认为与作用在系绳和受压微绒毛上的力协同平衡，然而，它们的相对贡献仍有待确定。因此，超出目前理解的改进需要可以预测细胞和微绒毛变形的计算机模型和允许测量作用于单个微绒毛和栓系的力的实验。
Leukocyte rolling on endothelial cells and other P-selectin substrates is mediated by P-selectin binding to P-selectin glycoprotein ligand-1 expressed on the tips of leukocyte microvilli. Leukocyte rolling is a result of rapid, yet balanced formation and dissociation of selectin-ligand bonds in the presence of hydrodynamic shear forces. The hydrodynamic forces acting on the bonds may either increase (catch bonds) or decrease (slip-bonds) their lifetimes. The force-dependent ‘catch-slip’ bond kinetics are explained using the ‘two pathway model’ for bond dissociation. Both the ‘sliding-rebinding’ and the ‘allosteric’ mechanisms attribute ‘catch-slip’ bond behavior to the force-induced conformational changes in the lectin-EGF domain hinge of selectins. Below a threshold shear stress, selectins cannot mediate rolling. This ‘shear-threshold’ phenomenon is a consequence of shear-enhanced tethering and catch-bond enhanced rolling. Quantitative dynamic footprinting microscopy has revealed that leukocytes rolling at venular shear stresses (> 0.6 Pa) undergo cellular deformation (large footprint) and form long tethers. The hydrodynamic shear force and torque acting on the rolling cell are thought to be synergistically balanced by the forces acting on tethers and stressed microvilli, however, their relative contribution remains to be determined. Thus, improvement beyond the current understanding requires in silico models that can predict both cellular and microvillus deformation and experiments that allow measurement of forces acting on individual microvilli and tethers.