Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Biophys J. 2010 Jan 6;98(1):37-47. doi: 10.1016/j.bpj.2009.10.002.
We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of tumor growth and invasion. The continuum part of the OLHDC model describes microenvironmental components such as matrix-degrading enzymes, nutrients or oxygen, and extracellular matrix (ECM) concentrations, whereas the discrete portion represents individual cell behavior such as cell cycle, cell-cell, and cell-ECM interactions and cell motility by the often-used persistent random walk, which can be depicted by the Langevin equation. Using this framework of the OLHDC model, we develop a phenomenologically realistic and bio/physically relevant model that encompasses the experimentally observed superdiffusive behavior (at short times) of mammalian cells. When systemic simulations based on the OLHDC model are performed, tumor growth and its morphology are found to be strongly affected by cell-cell adhesion and haptotaxis. There is a combination of the strength of cell-cell adhesion and haptotaxis in which fingerlike shapes, characteristic of invasive tumor, are observed.
我们开发了一种用于肿瘤生长和入侵的无网格混合离散连续（OLHDC）模型。OLHDC 模型的连续部分描述了基质降解酶、营养物质或氧气以及细胞外基质（ECM）浓度等微观环境成分，而离散部分则通过常用的持续随机游动来表示单个细胞的行为，如细胞周期、细胞-细胞和细胞-ECM 相互作用以及细胞迁移性，持续随机游动可以通过朗之万方程来描述。使用这种 OLHDC 模型框架，我们开发了一个具有物理意义的、包含实验观察到的哺乳动物细胞超扩散行为（短时间内）的、唯象逼真的模型。当基于 OLHDC 模型进行系统模拟时，发现细胞-细胞黏附和趋化性强烈影响肿瘤的生长和形态。在细胞-细胞黏附强度和趋化性的组合中，观察到了具有侵袭性肿瘤特征的指状形状。
