Khain Evgeniy, Katakowski Mark, Hopkins Scott, Szalad Alexandra, Zheng Xuguang, Jiang Feng, Chopp Michael
Department of Physics, Oakland University, Rochester, Michigan 48309, USA.
Phys Rev E Stat Nonlin Soft Matter Phys. 2011 Mar;83(3 Pt 1):031920. doi: 10.1103/PhysRevE.83.031920. Epub 2011 Mar 29.
We consider emergent collective behavior of a multicellular biological system. Specifically, we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. In the first set of experiments, cell migration away from a tumor spheroid was investigated. The second set of experiments was performed in a typical wound-healing geometry: Cells were placed on a substrate, a scratch was made, and cell migration into the gap was investigated. Experiments show a surprising result: Cells under normal and hypoxic conditions have migrated the same distance in the "spheroid" experiment, while in the "scratch" experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.
我们研究多细胞生物系统的涌现集体行为。具体而言，我们研究缺氧（氧气缺乏）在脑肿瘤细胞迁移中的作用。我们进行了两组细胞迁移实验。在第一组实验中，研究了细胞从肿瘤球体向外的迁移。第二组实验采用典型的伤口愈合模型进行：将细胞放置在基质上，制造划痕，然后研究细胞向间隙中的迁移。实验显示出一个惊人的结果：在“球体”实验中，正常条件和缺氧条件下的细胞迁移了相同的距离，而在“划痕”实验中，正常条件下的细胞迁移速度比缺氧条件下快得多。为了解释这一矛盾，我们为细胞动力学建立了一个离散随机模型。该理论模型解释了我们的实验观察结果，并表明缺氧会降低细胞的运动性和细胞间粘附力。理论预测在独立实验中得到了进一步验证。
