Cells competition in tumor growth poroelasticity
Cells competition in tumor growth poroelasticity
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DOI：
10.1016/j.jmps.2017.12.015
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发表时间：
2018-03-01
影响因子：
5.3
通讯作者：
Carotenuto, Angelo R.
中科院分区：
文献类型：
--
作者：
Fraldi, Massimiliano;Carotenuto, Angelo R.
近年来，在连续介质力学的框架内处理生物组织的生长，采用了非均匀孔弹性模型，其中软基质和间质流体之间的相互作用与特别引入的非弹性效应相耦合，以模拟由细胞分裂、细胞生长和细胞外基质在微观水平上发生的变化所决定的宏观体积生长。这些连续介质模型似乎克服了多相系统中基于质量平衡的其他替代方法固有的一些局限性，因为伴随生长和营养物质通道的残余应力所起的关键作用被保留了下来。然而，当这些策略被应用于分析实体肿瘤时，质量增长通常被指定为一种规定的形式，基本上复制了体外测量的细胞种类的固有增长率。其结果是，控制癌细胞质量演化和侵袭率的一些重要的细胞-细胞动力学，以及它们与与原位应力相关的反馈机制的耦合，不可避免地丢失了，因此肿瘤内部生长的空间分布和随时间的演变--这将是结果而不是输入--被迫作为数据进入模型。为了解决这一悖论，本文提出了一个改进的多尺度孔弹性模型，它经历了大变形并体现了非弹性生长，其中净增长项直接来自于在微观尺度上健康和异常细胞物种之间发生的“种间”捕食者-猎物(Volterra/Lotka)竞争。这样，一个完全耦合的非线性偏微分方程组被用来描述细胞物种之间争夺可用公共资源的斗争、应力场、压力梯度、驱动营养的间质流体流动以及非均匀生长如何同时相互作用来决定肿瘤的命运。(C)2018爱思唯尔有限公司。保留所有权利。
Growth of biological tissues has been recently treated within the framework of Continuum Mechanics, by adopting heterogeneous poroelastic models where the interaction between soft matrix and interstitial fluid flow is coupled with inelastic effects ad hoc introduced to simulate the macroscopic volumetric growth determined by cells division, cells growth and extracellular matrix changes occurring at the micro-scale level. These continuum models seem to overcome some limitations intrinsically associated to other alternative approaches based on mass balances in multiphase systems, because the crucial role played by residual stresses accompanying growth and nutrients walkway is preserved. Nevertheless, when these strategies are applied to analyze solid tumors, mass growth is usually assigned in a prescribed form that essentially copies the in vitro measured intrinsic growth rates of the cell species. As a consequence, some important cell-cell dynamics governing mass evolution and invasion rates of cancer cells, as well as their coupling with feedback mechanisms associated to in situ stresses, are inevitably lost and thus the spatial distribution and the evolution with time of the growth inside the tumor-which would be results rather than inputs- are forced to enter in the model simply as data. In order to solve this paradox, it is here proposed an enhanced multi-scale poroelastic model undergoing large deformations and embodying inelastic growth, where the net growth terms directly result from the "interspecific" predator-prey (Volterra/Lotka-like) competition occurring at the micro-scale level between healthy and abnormal cell species. In this way, a system of fully-coupled non-linear PDEs is derived to describe how the fight among cell species to grab the available common resources, stress field, pressure gradients, interstitial fluid flows driving nutrients and inhomogeneous growth all simultaneously interact to decide the tumor fate. (C) 2018 Elsevier Ltd. All rights reserved.