Mousavi S J, Doweidar M H, Doblaré M
Group of Structural Mechanics and Materials Modelling (GEMM), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.
Mol Cell Biomech. 2013 Mar;10(1):1-25.
Although there are several computational models that explain the trajectory that cells take during migration, till now little attention has been paid to the integration of the cell migration in a multi-signaling system. With that aim, a generalized model of cell migration and cell-cell interaction under multisignal environments is presented herein. In this work we investigate the spatio-temporal cell-cell interaction problem induced by mechano-chemo-thermotactic cues. It is assumed that formation of a new focal adhesion generates traction forces proportional to the stresses transmitted by the cell to the extracellular matrix. The cell velocity and polarization direction are calculated based on the equilibrium of the effective forces associated to cell motility. It is also assumed that, in addition to mechanotaxis signals, chemotactic and thermotactic cues control the direction of the resultant traction force. This model enables predicting the trajectory of migrating cells as well as the spatial and temporal distributions of the net traction force and cell velocity. Results indicate that the tendency of the cells is firstly to reach each other and then migrate towards an imaginary equilibrium plane located near the source of the signal. The position of this plane is sensitive to the gradient slope and the corresponding efficient factors. The cells come into contact and separate several times during migration. Adding other cues to the substrate (such as chemotaxis and/or thermotaxis) delays that primary contact. Moreover, in all states, the average local velocity and the net traction force of the cells decrease while the cells approach the cues source. Our findings are qualitatively consistent with experimental observations reported in the related literature.
尽管有几种计算模型可以解释细胞在迁移过程中所采取的轨迹,但迄今为止,细胞迁移在多信号系统中的整合问题几乎没有得到关注。出于这个目的,本文提出了一种多信号环境下细胞迁移和细胞间相互作用的通用模型。在这项工作中,我们研究了机械 - 化学 - 热趋化线索诱导的时空细胞间相互作用问题。假设新的粘着斑的形成产生与细胞传递到细胞外基质的应力成比例的牵引力。基于与细胞运动相关的有效力的平衡来计算细胞速度和极化方向。还假设,除了机械趋化信号外,化学趋化和热趋化线索控制合成牵引力的方向。该模型能够预测迁移细胞的轨迹以及净牵引力和细胞速度的空间和时间分布。结果表明,细胞的趋势首先是相互靠近,然后朝着位于信号源附近的假想平衡平面迁移。该平面的位置对梯度斜率和相应的有效因子敏感。细胞在迁移过程中会多次接触和分离。在底物中添加其他线索(如化学趋化和/或热趋化)会延迟初次接触。此外,在所有状态下,细胞接近线索源时,其平均局部速度和净牵引力都会降低。我们的发现与相关文献中报道的实验观察结果在定性上是一致的。