Division of Mathematical Biology, MRC National Institute for Medical Research, London, United Kingdom.
PLoS One. 2012;7(8):e43226. doi: 10.1371/journal.pone.0043226. Epub 2012 Aug 29.
From simulations that begin with a random mix of two cell types, we monitor progress towards segregation driven by contact-mediated linkage of model cells, which is equivalent to the cell-cell adhesion of real cells. In comparison with real cell experiments, we show that this mechanical model can account for the observed extent of segregation obtained by differential adhesion in a 2D cell culture assay of cells with differentially expressed cadherin molecules. Calibration of virtual to real time allowed us to estimate a time course for these experiments that was within 50% agreement for the simulations compared to differential adhesion of cells. In contrast, simulations of differential adhesion do not account for the rate of segregation driven by interactions between EphB2 receptor and ephrinB1 expressing cells which occurs an order of magnitude faster. The latter result suggests that mechanisms additional or alternative to differential adhesion contribute to Eph-ephrin mediated cell segregation.
从模拟开始，两种细胞类型随机混合，我们监测由模型细胞的接触介导的连接驱动的分离进展，这相当于真实细胞的细胞间粘附。与真实细胞实验相比，我们表明，这种机械模型可以解释在具有差异表达钙粘蛋白分子的二维细胞培养测定中通过差异粘附获得的观察到的分离程度。虚拟到实际时间的校准使我们能够估计这些实验的时间过程，与细胞的差异粘附相比，模拟结果的一致性在 50%以内。相比之下，差异粘附的模拟并不能解释 EphB2 受体和表达 EphrinB1 的细胞之间相互作用驱动的分离速率，这种分离速率快一个数量级。后一结果表明，除了差异粘附之外，还有其他机制或替代机制有助于 Eph-ephrin 介导的细胞分离。
