A data-driven approach to modeling cancer cell mechanics during microcirculatory transport.
A data-driven approach to modeling cancer cell mechanics during microcirculatory transport.
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DOI：
10.1038/s41598-021-94445-5
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发表时间：
2021-07-27
影响因子：
4.6
通讯作者：
Randles A
中科院分区：
文献类型：
--
作者：
Balogh P;Gounley J;Roychowdhury S;Randles A
为了了解细胞水平特征对微循环中循环癌细胞转运的影响，人们越来越依赖高分辨率的计算机模型。准确模拟癌细胞与血细胞的流动需要在3D中解决细胞尺度的相互作用，这是一项重要的计算任务，需要建立一个计算效率高但足够复杂的癌细胞模型来捕获相关行为。鉴于转移扩散的特征已知取决于癌症类型，因此解释代表特定癌症细胞的机械行为至关重要。为了解决这一差距，在目前的工作中，我们开发并验证了一种方法，通过这种方法，可以使用一种有效和流行的基于膜模型的方法来模拟可变形的癌细胞，并从特定的细胞系中重现实验数据。在这里，使用格子Boltzmann方法（LBM）流体求解器内的浸没边界方法（IBM）对细胞进行建模，并且使用有限元方法（FEM）对细胞膜的变形阻力进行建模。通过与实验的详细比较，我们（i）验证该模型代表经历大变形的癌细胞，（ii）概述了一种系统的方法来参数化不同的细胞系，以最佳地拟合一系列变形的实验数据，以及（iii）提供了新的见解有核与无核细胞模型及其匹配实验的能力。虽然许多工作已经使用了膜模型为基础的方法，在这里建模一般的癌细胞，没有定量比较与实验中存在的文献中的特定细胞系经历大变形。在这里，我们描述了一种现象学的，数据驱动的方法，不仅可以产生良好的协议，为大变形，但明确详细说明它如何可以用来代表不同的癌细胞系。该模型很容易纳入细胞分辨的血液动力学运输模拟，从而提供了重要的潜力，以补充实验，为癌症进展的各个方面提供新的见解。
In order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimental data over a range of deformations, and (iii) provide new insight into nucleated vs. non-nucleated cell models and their ability to match experiments. While many works have used the membrane-model based method employed here to model generic cancer cells, no quantitative comparisons with experiments exist in the literature for specific cell lines undergoing large deformation. Here, we describe a phenomenological, data-driven approach that can not only yield good agreement for large deformations, but explicitly detail how it can be used to represent different cancer cell lines. This model is readily incorporated into cell-resolved hemodynamic transport simulations, and thus offers significant potential to complement experiments towards providing new insights into various aspects of cancer progression.
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影响因子：
--
作者：
Denais C;Lammerding J
通讯作者：
Lammerding J
影响因子：
3.7
作者：
Dabagh, Mahsa;Randles, Amanda
通讯作者：
Randles, Amanda
影响因子：
4.1
作者：
Agresar, G;Linderman, JJ;Powell, KG
通讯作者：
Powell, KG
DOI：
10.1073/pnas.1524448113
发表时间：
2016-05-03
影响因子：
11.1
作者：
Au, Sam H.;Storey, Brian D.;Toner, Mehmet
通讯作者：
Toner, Mehmet
影响因子：
3.7
作者：
Barthès-Biesel, D;Diaz, A;Dhenin, E
通讯作者：
Dhenin, E