Varennes Julien, Han Bumsoo, Mugler Andrew
Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana.
Schools of Mechanical Engineering and Biomedical Engineering, Purdue University, West Lafayette, Indiana; Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana.
Biophys J. 2016 Aug 9;111(3):640-649. doi: 10.1016/j.bpj.2016.06.040.
Collective cell migration in response to a chemical cue occurs in many biological processes such as morphogenesis and cancer metastasis. Clusters of migratory cells in these systems are capable of responding to gradients of <1% difference in chemical concentration across a cell length. Multicellular systems are extremely sensitive to their environment, and although the limits to multicellular sensing are becoming known, how this information leads to coherent migration remains poorly understood. We develop a computational model of multicellular sensing and migration in which groups of cells collectively measure noisy chemical gradients. The output of the sensing process is coupled to the polarization of individual cells to model migratory behavior. Through the use of numerical simulations, we find that larger clusters of cells detect the gradient direction with higher precision and thus achieve stronger polarization bias, but larger clusters also induce more drag on collective motion. The trade-off between these two effects leads to an optimal cluster size for most efficient migration. We discuss how our model could be validated using simple, phenomenological experiments.
响应化学信号的集体细胞迁移发生在许多生物过程中,如形态发生和癌症转移。在这些系统中,迁移细胞簇能够响应跨细胞长度化学浓度差异小于1%的梯度。多细胞系统对其环境极其敏感,尽管多细胞感知的极限正在为人所知,但这种信息如何导致协调一致的迁移仍知之甚少。我们开发了一个多细胞感知和迁移的计算模型,其中细胞群集体测量有噪声的化学梯度。感知过程的输出与单个细胞的极化相耦合,以模拟迁移行为。通过数值模拟,我们发现更大的细胞簇能以更高的精度检测梯度方向,从而实现更强的极化偏差,但更大的细胞簇也会对集体运动产生更大的阻力。这两种效应之间的权衡导致了最有效迁移的最佳簇大小。我们讨论了如何使用简单的现象学实验来验证我们的模型。