基于参数化数学模型的微流控系统循环肿瘤细胞结合解译。

IF 1.9 4区 数学 Q2 BIOLOGY Journal of Theoretical Biology Pub Date : 2024-12-16 DOI:10.1016/j.jtbi.2024.112029
Giorgia Ciavolella , Julien Granet , Jacky G. Goetz , Naël Osmani , Christèle Etchegaray , Annabelle Collin
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引用次数: 0

摘要

转移的扩散是一个关键的过程,其中一些问题仍未得到解答。在这项工作中,我们专注于在血液中循环的肿瘤细胞,即所谓的循环肿瘤细胞(CTCs)。我们的目的是表征它们在血流动力学和粘附力影响下的轨迹。我们专注于已经可用的体外测量,使用微流控装置进行相应的ctc轨迹-没有或具有不同的蛋白质消耗-与内皮层相互作用。一个关键的困难是对必须重建的流体速度知之甚少。我们的策略结合了微分方程模型-流体速度的泊泽维尔模型和细胞粘附模型的ODE系统-以及稳健且精心设计的校准程序。参数化模型量化了流体速度对黏附的强烈影响,并证实了几种蛋白质在ctc减速中的预期作用。最后,即使在未观察到的实验条件下,它也能生成合成细胞,为具有粘附性的流动细胞的数字双胞胎开辟了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model
The spread of metastases is a crucial process in which some questions remain unanswered. In this work, we focus on tumor cells circulating in the bloodstream, the so-called Circulating Tumor Cells (CTCs). Our aim is to characterize their trajectories under the influence of hemodynamic and adhesion forces. We focus on already available in vitro measurements performed with a microfluidic device corresponding to the trajectories of CTCs – without or with different protein depletions – interacting with an endothelial layer. A key difficulty is the weak knowledge of the fluid velocity that has to be reconstructed. Our strategy combines a differential equation model – a Poiseuille model for the fluid velocity and an ODE system for the cell adhesion model – and a robust and well-designed calibration procedure. The parameterized model quantifies the strong influence of fluid velocity on adhesion and confirms the expected role of several proteins in the deceleration of CTCs. Finally, it enables the generation of synthetic cells, even for unobserved experimental conditions, opening the way to a digital twin for flowing cells with adhesion.
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来源期刊
CiteScore
4.20
自引率
5.00%
发文量
218
审稿时长
51 days
期刊介绍: The Journal of Theoretical Biology is the leading forum for theoretical perspectives that give insight into biological processes. It covers a very wide range of topics and is of interest to biologists in many areas of research, including: • Brain and Neuroscience • Cancer Growth and Treatment • Cell Biology • Developmental Biology • Ecology • Evolution • Immunology, • Infectious and non-infectious Diseases, • Mathematical, Computational, Biophysical and Statistical Modeling • Microbiology, Molecular Biology, and Biochemistry • Networks and Complex Systems • Physiology • Pharmacodynamics • Animal Behavior and Game Theory Acceptable papers are those that bear significant importance on the biology per se being presented, and not on the mathematical analysis. Papers that include some data or experimental material bearing on theory will be considered, including those that contain comparative study, statistical data analysis, mathematical proof, computer simulations, experiments, field observations, or even philosophical arguments, which are all methods to support or reject theoretical ideas. However, there should be a concerted effort to make papers intelligible to biologists in the chosen field.
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