The state diagram for cell adhesion under flow: Leukocyte rolling and firm adhesion
The state diagram for cell adhesion under flow: Leukocyte rolling and firm adhesion
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DOI：
10.1073/pnas.200240897
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Hammer, DA
中科院分区：
文献类型：
--
作者：
Chang, KC;Tees, DFJ;Hammer, DA
微血管系统中流动下的白细胞粘附通过细胞表面受体与内皮表面上表达的互补配体之间的结合介导。白细胞以两步机制粘附于内皮：滚动（主要由选择素介导），然后牢固粘附（主要由整联蛋白介导）。使用一种叫做“粘附动力学”的计算方法。“我们模拟了细胞在流动中粘附到表面，并阐明了受体-配体功能特性和粘附动力学之间的关系。我们用状态图来表达这种关系，这是粘附分子的生物物理特性和各种粘附行为之间的一对一映射。在模拟中观察到的行为包括牢固粘附、瞬时粘附（滚动）和无粘附。我们改变的解离特性，缔合速率，键弹性，和剪切速率，并发现，无应力的解离速率，k（r）（o），和键的相互作用长度，γ，是最重要的分子特性控制的动态粘附。已知介导滚动粘附的分子的文献中的实验k（r）（o）和γ值落在状态图的滚动区域内。我们解释了为什么L-选择素介导的滚动，它具有更快的k（r）（o）比其他选择素，是伴随着一个较小的γ值。我们还展示了缔合速率、剪切速率和键弹性的变化如何改变粘附的动力学。状态图（必须映射为每个受体-配体系统）提出了一个简洁而全面的理解键的功能特性和受体-配体键介导的粘附动力学之间的关系的手段。
Leukocyte adhesion under flow in the microvasculature is mediated by binding between cell surface receptors and complementary ligands expressed on the surface of the endothelium. Leukocytes adhere to endothelium in a two-step mechanism: rolling (primarily mediated by selectins) followed by firm adhesion (primarily mediated by integrins). Using a computational method called "Adhesive Dynamics." we have simulated the adhesion of a cell to a surface in flow, and elucidated the relationship between receptor-ligand functional properties and the dynamics of adhesion. We express this relationship in a state diagram, a one-to-one map between the biophysical properties of adhesion molecules and various adhesive behaviors. Behaviors that are observed in simulations include firm adhesion, transient adhesion (rolling), and no adhesion. We varied the dissociative properties, association rate, bond elasticity, and shear rate and found that the unstressed dissociation rate, k(r)(o), and the bond interaction length, gamma, are the most important molecular properties controlling the dynamics of adhesion. Experimental k(r)(o) and gamma values from the literature for molecules that are known to mediate rolling adhesion fall within the rolling region of the state diagram. We explain why L-selectin-mediated rolling, which has faster k(r)(o) than other selectins, is accompanied by a smaller Value for gamma. We also show how changes in association rate, shear rate, and bond elasticity alter the dynamics of adhesion. The state diagram (which must be mapped for each receptor-ligand system) presents a concise and comprehensive means of understanding the relationship between bond functional properties and the dynamics of adhesion mediated by receptor-ligand bonds.