Department of Bioengineering, University of Pennsylvania, 19104, USA.
J Theor Biol. 2009 Sep 7;260(1):27-30. doi: 10.1016/j.jtbi.2009.05.014. Epub 2009 May 30.
Here we accurately recreate the mechanical shedding of L-selectin and its effect on the rolling behavior of neutrophils in vitro using the adhesive dynamics simulation by incorporating the shear-dependent shedding of L-selectin. We have previously shown that constitutively expressed L-selectin is cleaved from the neutrophil surface during rolling on a sialyl Lewis x-coated planar surface at physiological shear rates without the addition of exogenous stimuli. Utilizing a Bell-like model to describe a shedding rate which presumably increases exponentially with force, we were able to reconstruct the characteristics of L-selectin-mediated neutrophil rolling observed in the experiments. First, the rolling velocity was found to increase during rolling due to the mechanical shedding of L-selectin. When most of the L-selectin concentrated on the tips of deformable microvilli was cleaved by force exerted on the L-selectin bonds, the cell detached from the reactive plane to join the free stream as observed in the experiments. In summary, we show through detailed computational modeling that the force-dependent shedding of L-selectin can explain the rolling behavior of neutrophils mediated by L-selectin in vitro.
在这里，我们通过结合剪切依赖性的 L-选择素脱落，使用粘附动力学模拟，准确地再现了 L-选择素的机械脱落及其对体外中性粒细胞滚动行为的影响。我们之前已经表明，在生理剪切速率下，在唾液酸化 Lewis x 涂层的平面表面上滚动时，固有表达的 L-选择素会从中性粒细胞表面脱落，而无需添加外源性刺激。利用钟形模型来描述脱落率，推测脱落率随力呈指数增长，我们能够重建实验中观察到的 L-选择素介导的中性粒细胞滚动的特征。首先，由于 L-选择素的机械脱落，发现滚动速度在滚动过程中增加。当 L-选择素结合物上的力将集中在可变形微绒毛尖端的大多数 L-选择素切断时，细胞就会像实验中观察到的那样从反应平面上脱离，加入自由流。总之，我们通过详细的计算模型表明，L-选择素的力依赖性脱落可以解释体外 L-选择素介导的中性粒细胞滚动行为。
