Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America.
PLoS One. 2011;6(5):e20182. doi: 10.1371/journal.pone.0020182. Epub 2011 May 25.
Cells organize in complex three-dimensional patterns by interacting with proteins along with the surrounding extracellular matrix. This organization provides the mechanical and chemical cues that ultimately influence a cell's differentiation and function. Here, we computationally investigate the pattern formation process of vascular mesenchymal cells arising from their interaction with Bone Morphogenic Protein-2 (BMP-2) and its inhibitor, Matrix Gla Protein (MGP). Using a first-principles approach, we derive a reaction-diffusion model based on the biochemical interactions of BMP-2, MGP and cells. Simulations of the model exhibit a wide variety of three-dimensional patterns not observed in a two-dimensional analysis. We demonstrate the emergence of three types of patterns: spheres, tubes, and sheets, and show that the patterns can be tuned by modifying parameters in the model such as the degradation rates of proteins and chemotactic coefficient of cells. Our model may be useful for improved engineering of three-dimensional tissue structures as well as for understanding three dimensional microenvironments in developmental processes.
细胞通过与蛋白质以及周围的细胞外基质相互作用,组织成复杂的三维模式。这种组织为细胞的分化和功能提供了最终影响的机械和化学线索。在这里,我们通过计算方法研究了血管间充质细胞从与骨形态发生蛋白 2(BMP-2)及其抑制剂基质 Gla 蛋白(MGP)相互作用中形成模式的过程。我们使用一种基于 BMP-2、MGP 和细胞生化相互作用的第一性原理方法,推导出了一个反应-扩散模型。该模型的模拟显示了在二维分析中观察不到的各种三维模式。我们展示了三种类型的模式:球体、管和片,并表明可以通过修改模型中的参数来调整模式,例如蛋白质的降解率和细胞的趋化系数。我们的模型可能有助于改进三维组织结构的工程设计,以及理解发育过程中的三维微环境。