应用于癌细胞诱导的细胞外基质降解的三维牵引力显微镜多物理场建模

IF 8.7 2区 工程技术 Q1 Mathematics
Alejandro Apolinar-Fernández, Jorge Barrasa-Fano, Hans Van Oosterwyck, José A. Sanz-Herrera
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引用次数: 0

摘要

三维牵引力显微镜(3DTFM)是一种功能强大的方法,可以计算细胞对周围细胞外基质(ECM)施加的真实作用力。细胞外基质具有高度动态结构的特点,它不断重塑以调节大多数基本细胞功能和过程。某些病理过程,如癌症和转移,会改变 ECM 的重塑方式。特别是,癌细胞能够通过分泌金属蛋白酶降解细胞外基质来侵袭周围组织,从而向不同组织移动和迁移,诱发 ECM 异质性。通常情况下,3DTFM 研究忽略了这种异质性,并假设 ECM 属性是均质的,这可能导致牵引重建不准确。一些研究在 3DTFM 中采用了 ECM 降解模型,但相关的降解图都是临时定义的。在本文中,我们提出了一种新颖的多物理场 3DTFM 方法,该方法具有不断变化的 ECM 机械特性。我们的建模考虑了基于膜结合金属蛋白酶 MT1-MMP 激活扩散金属蛋白酶 MMP2 机制的偏微分方程系统。得到的 ECM 模拟水凝胶中的 ECM 密度图可用于通过多尺度方法计算水凝胶的异质机械性能。我们进行了考虑降解和不考虑降解的正向和反向 TFM 模拟,并将结果与考虑降解的地面实况参考方案进行了比较。研究得出的主要结论是(i) 逆向方法得出的结果比正向方法得出的结果要精确得多;(ii) 忽略 ECM 降解会导致对牵引力的高估,并且在所有分析案例中都会产生不可忽略的误差。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multiphysics modeling of 3D traction force microscopy with application to cancer cell-induced degradation of the extracellular matrix

Multiphysics modeling of 3D traction force microscopy with application to cancer cell-induced degradation of the extracellular matrix

3D Traction Force Microscopy (3DTFM) constitutes a powerful methodology that enables the computation of realistic forces exerted by cells on the surrounding extracellular matrix (ECM). The ECM is characterized by its highly dynamic structure, which is constantly remodeled in order to regulate most basic cellular functions and processes. Certain pathological processes, such as cancer and metastasis, alter the way the ECM is remodeled. In particular, cancer cells are able to invade its surrounding tissue by the secretion of metalloproteinases that degrade the extracellular matrix to move and migrate towards different tissues, inducing ECM heterogeneity. Typically, 3DTFM studies neglect such heterogeneity and assume homogeneous ECM properties, which can lead to inaccuracies in traction reconstruction. Some studies have implemented ECM degradation models into 3DTFM, but the associated degradation maps are defined in an ad hoc manner. In this paper, we present a novel multiphysics approach to 3DTFM with evolving mechanical properties of the ECM. Our modeling considers a system of partial differential equations based on the mechanisms of activation of diffusive metalloproteinase MMP2 by membrane-bound metalloproteinase MT1-MMP. The obtained ECM density maps in an ECM-mimicking hydrogel are then used to compute the heterogeneous mechanical properties of the hydrogel through a multiscale approach. We perform forward and inverse TFM simulations both accounting for and omitting degradation, and results are compared to ground truth reference solutions in which degradation is considered. The main conclusions resulting from the study are: (i) the inverse methodology yields results that are significantly more accurate than those provided by the forward methodology; (ii) ignoring ECM degradation results in a considerable overestimation of tractions and non negligible errors in all analyzed cases.

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来源期刊
Engineering with Computers
Engineering with Computers 工程技术-工程:机械
CiteScore
16.50
自引率
2.30%
发文量
203
审稿时长
9 months
期刊介绍: Engineering with Computers is an international journal dedicated to simulation-based engineering. It features original papers and comprehensive reviews on technologies supporting simulation-based engineering, along with demonstrations of operational simulation-based engineering systems. The journal covers various technical areas such as adaptive simulation techniques, engineering databases, CAD geometry integration, mesh generation, parallel simulation methods, simulation frameworks, user interface technologies, and visualization techniques. It also encompasses a wide range of application areas where engineering technologies are applied, spanning from automotive industry applications to medical device design.
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