Sircar Sarthok, Roberts Anthony J
University of Adelaide, 650 Ingkarni Wardli Bldg, Adelaide, SA, 5005, Australia.
University of Adelaide, 738 Ingkarni Wardli Bldg, Adelaide, SA, 5005, Australia.
J Math Biol. 2016 Oct;73(4):1035-52. doi: 10.1007/s00285-016-0983-7. Epub 2016 Mar 10.
We present a unified, multiscale model to study the attachment/detachment dynamics of two deforming, charged, near spherical cells, coated with binding ligands and subject to a slow, homogeneous shear flow in a viscous, ionic fluid medium. The binding ligands on the surface of the cells experience both attractive and repulsive forces in an ionic medium and exhibit finite resistance to rotation via bond tilting. The microscale drag forces and couples describing the fluid flow inside the small separation gap between the cells, are calculated using a combination of methods in lubrication theory and previously published numerical results. For a selected range of material and fluid parameters, a hysteretic transition of the sticking probability curves (i.e., the function [Formula: see text]) between the adhesion phase (when [Formula: see text]) and the fragmentation phase (when [Formula: see text]) is attributed to a nonlinear relation between the total nanoscale binding forces and the separation gap between the cells. We show that adhesion is favoured in highly ionic fluids, increased deformability of the cells, elastic binders and a higher fluid shear rate (until a critical threshold value of shear rate is reached). Within a selected range of critical shear rates, the continuation of the limit points (i.e., the turning points where the slope of [Formula: see text] changes sign) predict a bistable region, indicating an abrupt switching between the adhesion and the fragmentation regimes. Although, bistability in the adhesion-fragmentation phase diagram of two deformable, charged cells immersed in an ionic aqueous environment has been identified by some in vitro experiments, but until now, has not been quantified theoretically.
我们提出了一个统一的多尺度模型,用于研究两个变形、带电的近球形细胞的附着/分离动力学。这两个细胞表面涂有结合配体,并在粘性离子流体介质中受到缓慢、均匀的剪切流作用。细胞表面的结合配体在离子介质中同时受到吸引力和排斥力,并且通过键倾斜对旋转表现出有限的阻力。描述细胞间小分离间隙内流体流动的微观尺度阻力和力偶,是使用润滑理论中的方法和先前发表的数值结果相结合来计算的。对于选定的材料和流体参数范围,粘附概率曲线(即函数[公式:见原文])在粘附阶段(当[公式:见原文])和破碎阶段(当[公式:见原文])之间的滞后转变,归因于总纳米尺度结合力与细胞间分离间隙之间的非线性关系。我们表明,在高离子流体、细胞可变形性增加、弹性粘合剂以及较高的流体剪切速率(直到达到剪切速率的临界阈值)的情况下,粘附更有利。在选定的临界剪切速率范围内,极限点(即[公式:见原文]斜率改变符号的转折点)的延续预测了一个双稳区域,表明在粘附和破碎状态之间会突然切换。尽管一些体外实验已经确定了浸入离子水环境中的两个可变形带电细胞的粘附 - 破碎相图中的双稳性,但到目前为止,尚未从理论上进行量化。