Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana 47907, USA.
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Phys Rev E. 2021 Mar;103(3-1):032410. doi: 10.1103/PhysRevE.103.032410.
Collections of cells exhibit coherent migration during morphogenesis, cancer metastasis, and wound healing. In many cases, bigger clusters split, smaller subclusters collide and reassemble, and gaps continually emerge. The connections between cell-level adhesion and cluster-level dynamics, as well as the resulting consequences for cluster properties such as migration velocity, remain poorly understood. Here we investigate collective migration of one- and two-dimensional cell clusters that collectively track chemical gradients using a mechanism based on contact inhibition of locomotion. We develop both a minimal description based on the lattice gas model of statistical physics and a more realistic framework based on the cellular Potts model which captures cell shape changes and cluster rearrangement. In both cases, we find that cells have an optimal adhesion strength that maximizes cluster migration speed. The optimum negotiates a tradeoff between maintaining cell-cell contact and maintaining configurational freedom, and we identify maximal variability in the cluster aspect ratio as a revealing signature. Our results suggest a collective benefit for intermediate cell-cell adhesion.
细胞集合在形态发生、癌症转移和伤口愈合过程中表现出一致的迁移。在许多情况下,较大的集群会分裂,较小的亚集群会碰撞和重新组合,并且不断出现间隙。细胞水平的黏附与集群水平动力学之间的联系,以及对集群属性(如迁移速度)的结果仍知之甚少。在这里,我们研究了使用基于接触抑制运动的机制来集体跟踪化学梯度的一维和二维细胞集群的集体迁移。我们开发了一种基于统计物理学格子气模型的最小描述,以及一种更基于细胞 Potts 模型的更现实的框架,该模型可以捕捉细胞形状变化和集群重新排列。在这两种情况下,我们发现细胞具有最佳的黏附强度,可以最大程度地提高集群迁移速度。最优值在保持细胞间接触和保持构象自由度之间进行权衡,我们确定集群纵横比的最大可变性是一个明显的特征。我们的结果表明,中等的细胞间黏附具有集体优势。