Neagu Adrian, Mironov Vladimir, Kosztin Ioan, Barz Bogdan, Neagu Monica, Moreno-Rodriguez Ricardo A, Markwald Roger R, Forgacs Gabor
Department of Physics, University of Missouri, Columbia, MO 65211, USA.
Biosystems. 2010 Apr;100(1):23-30. doi: 10.1016/j.biosystems.2009.12.004. Epub 2009 Dec 31.
An epithelial-mesenchymal transformation (EMT) involves alterations in cell-cell and cell-matrix adhesion, the detachment of epithelial cells from their neighbors, the degradation of the basal lamina and acquisition of mesenchymal phenotype. Here we present Monte Carlo simulations for a specific EMT in early heart development: the formation of cardiac cushions. Cell rearrangements are described in accordance with Steinberg's differential adhesion hypothesis, which states that cells possess a type-dependent adhesion apparatus and are sufficiently motile to give rise to the tissue conformation with the largest number of strong bonds. We also implement epithelial and mesenchymal cell proliferation, cell type change and extracellular matrix production by mesenchymal cells. Our results show that an EMT is promoted more efficiently by an increase in cell-substrate adhesion than by a decrease in cell-cell adhesion. In addition to cushion tissue formation, the model also accounts for the phenomena of matrix invasion and mesenchymal condensation. We conclude that in order to maintain epithelial integrity during EMT the number of epithelial cells must increase at a controlled rate. Our model predictions are in qualitative agreement with available experimental data.
上皮-间质转化（EMT）涉及细胞间和细胞与基质黏附的改变、上皮细胞与其相邻细胞的脱离、基膜的降解以及间质表型的获得。在此，我们针对心脏早期发育过程中的一种特定上皮-间质转化——心脏心垫的形成，进行了蒙特卡洛模拟。细胞重排是根据斯坦伯格的差异黏附假说进行描述的，该假说指出细胞拥有依赖类型的黏附装置，并且具有足够的运动能力，从而形成具有最多强键的组织构象。我们还实现了上皮细胞和间质细胞的增殖、细胞类型的改变以及间质细胞产生细胞外基质。我们的结果表明，相比于细胞间黏附的降低，细胞与底物黏附的增加能更有效地促进上皮-间质转化。除了心垫组织的形成，该模型还解释了基质侵袭和间质凝聚现象。我们得出结论，为了在EMT过程中维持上皮完整性，上皮细胞的数量必须以可控的速率增加。我们的模型预测与现有实验数据在定性上是一致的。
