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首页> 美国卫生研究院文献>Biophysical Journal >A 3-D Computational Model Predicts that Cell Deformation Affects Selectin-Mediated Leukocyte Rolling
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A 3-D Computational Model Predicts that Cell Deformation Affects Selectin-Mediated Leukocyte Rolling

机译：3-D计算模型预测细胞变形影响Selectin介导的白细胞滚动

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Leukocyte recruitment to sites of inflammation is initiated by their tethering and rolling on the activated endothelium under flow. Even though the fast kinetics and high tensile strength of selectin-ligand bonds are primarily responsible for leukocyte rolling, experimental evidence suggests that cellular properties such as cell deformability and microvillus elasticity actively modulate leukocyte rolling behavior. Previous theoretical models either assumed cells as rigid spheres or were limited to two-dimensional representations of deformable cells with deterministic receptor-ligand kinetics, thereby failing to accurately predict leukocyte rolling. We therefore developed a three-dimensional computational model based on the immersed boundary method to predict receptor-mediated rolling of deformable cells in shear flow coupled to a Monte Carlo method simulating the stochastic receptor-ligand interactions. Our model predicts for the first time that the rolling of more compliant cells is relatively smoother and slower compared to cells with stiffer membranes, due to increased cell-substrate contact area. At the molecular level, we show that the average number of bonds per cell as well as per single microvillus decreases with increasing membrane stiffness. Moreover, the average bond lifetime decreases with increasing shear rate and with increasing membrane stiffness, due to higher hydrodynamic force experienced by the cell. Taken together, our model captures the effect of cellular properties on the coupling between hydrodynamic and receptor-ligand bond forces, and successfully explains the stable leukocyte rolling at a wide range of shear rates over that of rigid microspheres.
机译：白细胞募集到炎症部位是通过它们的束缚并在流动下在活化的内皮上滚动而开始的。尽管选择素-配体键的快速动力学和高拉伸强度是白细胞滚动的主要原因，但实验证据表明，诸如细胞可变形性和微绒毛弹性之类的细胞特性可主动调节白细胞滚动行为。先前的理论模型要么将细胞假定为刚性球体，要么将其限于具有确定性受体-配体动力学的可变形细胞的二维表示，从而无法准确预测白细胞的滚动。因此，我们开发了基于沉浸边界方法的三维计算模型，以预测剪切流中可变形细胞的受体介导的滚动，并耦合了模拟随机受体-配体相互作用的蒙特卡洛方法。我们的模型首次预测，由于细胞与基质的接触面积增加，与具有较硬膜的细胞相比，顺应性细胞的滚动相对更平稳，更慢。在分子水平上，我们显示每个细胞以及每个单个绒毛的平均键数随膜硬度的增加而降低。而且，由于电池所经受的较高的流体动力，平均键的寿命随着剪切速率的增加和膜硬度的增加而降低。综上所述，我们的模型捕获了细胞特性对流体动力学和受体-配体键合力之间耦合的影响，并成功地解释了在较刚性微球体大的剪切速率下稳定的白细胞滚动。

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