Localized Modeling of Biochemical and Flow Interactions during Cancer Cell Adhesion.
Localized Modeling of Biochemical and Flow Interactions during Cancer Cell Adhesion.
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DOI：
10.1371/journal.pone.0136926
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kunz R
中科院分区：
文献类型：
--
作者：
Behr J;Gaskin B;Fu C;Dong C;Kunz R
这项工作的重点是一个更大的研究工作的一个组成部分，即开发一个模拟工具来模拟流动细胞的群体。具体而言，本研究建立了循环黑色素瘤肿瘤细胞（TC）与底物粘附多形核中性粒细胞（PMN）之间生化相互作用的局部模型。该模型提供了真实的键形成和伴随的吸引力和排斥力的三维分布，与考虑局部压力、剪切和排斥力的全系统模型的时间依赖计算流体动力学（CFD）框架一致。由此产生的全动力学模型可以探索TC与粘附PMNs的粘附，这是黑色素瘤细胞转移的已知参与机制。该模型定义了TC和PMN细胞表面的粘附分子，并计算了黑色素瘤细胞流过PMN时它们之间的相互作用。单个分子之间反应的生化速率是根据它们的局部性质决定的。模型中的黑色素瘤细胞表面表达ICAM-1分子，PMN表面表达β-2整合素LFA-1和Mac-1。在这项工作中，PMN固定在衬底上，并假设完全刚性，并且具有从微piv实验中获得的规定剪切率相关形状。黑色素瘤细胞以完整的六自由度动态运输。黏附模型（表示分子结合和细胞相互粘附的能力）和斥力模型（表示细胞排斥的各种物理机制）被纳入CFD求解器中。所有模型都是通用的，足以允许未来的扩展，包括任意粘附分子类型，以及重新定义参数值以表示各种细胞类型的能力。本研究所提出的模型将会成为个人化医疗方案发展的临床工具的一部分。
This work focuses on one component of a larger research effort to develop a simulation tool to model populations of flowing cells. Specifically, in this study a local model of the biochemical interactions between circulating melanoma tumor cells (TC) and substrate adherent polymorphonuclear neutrophils (PMN) is developed. This model provides realistic three-dimensional distributions of bond formation and attendant attraction and repulsion forces that are consistent with the time dependent Computational Fluid Dynamics (CFD) framework of the full system model which accounts local pressure, shear and repulsion forces. The resulting full dynamics model enables exploration of TC adhesion to adherent PMNs, which is a known participating mechanism in melanoma cell metastasis. The model defines the adhesion molecules present on the TC and PMN cell surfaces, and calculates their interactions as the melanoma cell flows past the PMN. Biochemical rates of reactions between individual molecules are determined based on their local properties. The melanoma cell in the model expresses ICAM-1 molecules on its surface, and the PMN expresses the β-2 integrins LFA-1 and Mac-1. In this work the PMN is fixed to the substrate and is assumed fully rigid and of a prescribed shear-rate dependent shape obtained from micro-PIV experiments. The melanoma cell is transported with full six-degrees-of-freedom dynamics. Adhesion models, which represent the ability of molecules to bond and adhere the cells to each other, and repulsion models, which represent the various physical mechanisms of cellular repulsion, are incorporated with the CFD solver. All models are general enough to allow for future extensions, including arbitrary adhesion molecule types, and the ability to redefine the values of parameters to represent various cell types. The model presented in this study will be part of a clinical tool for development of personalized medical treatment programs.