Ribeiro F O, Gómez-Benito M J, Folgado J, Fernandes P R, García-Aznar J M
a IDMEC , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
b Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering , Universidad de Zaragoza , Zaragoza , Spain.
Comput Methods Biomech Biomed Engin. 2017 Jan;20(1):59-74. doi: 10.1080/10255842.2016.1198784. Epub 2016 Jun 23.
Cell chemotaxis is an important characteristic of cellular migration, which takes part in crucial aspects of life and development. In this work, we propose a novel in silico model of mesenchymal 3D migration with competing protrusions under a chemotactic gradient. Based on recent experimental observations, we identify three main stages that can regulate mesenchymal chemotaxis: chemosensing, dendritic protrusion dynamics and cell-matrix interactions. Therefore, each of these features is considered as a different module of the main regulatory computational algorithm. The numerical model was particularized for the case of fibroblast chemotaxis under a PDGF-bb gradient. Fibroblasts migration was simulated embedded in two different 3D matrices - collagen and fibrin - and under several PDGF-bb concentrations. Validation of the model results was provided through qualitative and quantitative comparison with in vitro studies. Our numerical predictions of cell trajectories and speeds were within the measured in vitro ranges in both collagen and fibrin matrices. Although in fibrin, the migration speed of fibroblasts is very low, because fibrin is a stiffer and more entangling matrix. Testing PDGF-bb concentrations, we noticed that an increment of this factor produces a speed increment. At 1 ng mL a speed peak is reached after which the migration speed diminishes again. Moreover, we observed that fibrin exerts a dampening behavior on migration, significantly affecting the migration efficiency.
细胞趋化性是细胞迁移的一个重要特征，它参与生命和发育的关键环节。在这项工作中，我们提出了一种新的计算机模拟模型，用于研究在趋化梯度下具有竞争性突起的间充质三维迁移。基于最近的实验观察，我们确定了可以调节间充质趋化性的三个主要阶段：化学感应、树突状突起动力学和细胞-基质相互作用。因此，这些特征中的每一个都被视为主要调节计算算法的不同模块。该数值模型针对血小板衍生生长因子-BB（PDGF-bb）梯度下成纤维细胞趋化性的情况进行了具体化。模拟了成纤维细胞在两种不同的三维基质——胶原蛋白和纤维蛋白——中以及在几种PDGF-bb浓度下的迁移。通过与体外研究进行定性和定量比较，对模型结果进行了验证。我们对细胞轨迹和速度的数值预测在胶原蛋白和纤维蛋白基质的体外测量范围内。尽管在纤维蛋白中，成纤维细胞的迁移速度非常低，因为纤维蛋白是一种更硬且更缠结的基质。测试PDGF-bb浓度时，我们注意到该因子的增加会导致速度增加。在1 ng/mL时达到速度峰值，之后迁移速度再次降低。此外，我们观察到纤维蛋白对迁移具有抑制作用，显著影响迁移效率。
