Takeishi Naoki, Imai Yohsuke, Ishida Shunichi, Omori Toshihiro, Kamm Roger D, Ishikawa Takuji
Graduate School of Biomedical Engineering, Tohoku University, Aoba, Sendai, Japan;
School of Engineering, Tohoku University, Aoba, Sendai, Japan;
Am J Physiol Heart Circ Physiol. 2016 Aug 1;311(2):H395-403. doi: 10.1152/ajpheart.00241.2016. Epub 2016 Jun 3.
A numerical analysis is presented of cell adhesion in capillaries whose diameter is comparable to or smaller than that of the cell. In contrast to a large number of previous efforts on leukocyte and tumor cell rolling, much is still unknown about cell motion in capillaries. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram was obtained for various values of capillary diameter and receptor density. We found that bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis.
本文对直径与细胞相当或小于细胞直径的毛细血管中的细胞黏附进行了数值分析。与此前大量关于白细胞和肿瘤细胞滚动的研究不同,关于细胞在毛细血管中的运动仍有许多未知之处。将流动中细胞的固体和流体力学与配体 - 受体相互作用的滑动键模型相结合。当毛细血管尺寸减小时,细胞总是转变为“子弹状”运动,导致细胞速度降低。得到了不同毛细血管直径和受体密度值的状态图。我们发现,即使配体 - 受体结合较弱,子弹状运动也能使细胞牢固黏附于毛细血管壁。我们还量化了各种参数的影响,包括解离速率常数、弹簧常数和反应性顺应性对细胞运动特性的影响。我们的结果表明,即使在主要负责白细胞滚动的P - 选择素糖蛋白配体 - 1(PSGL - 1)与P - 选择素之间的相互作用下,细胞在小毛细血管中也能够表现出牢固黏附。这些发现可能有助于理解白细胞阻塞和癌症转移等现象。