Department of Applied Physics, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
Department of Applied Physics, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
Biophys J. 2021 Apr 20;120(8):1483-1497. doi: 10.1016/j.bpj.2021.02.014. Epub 2021 Feb 20.
Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and in disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells moving as a coherent unit, has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: cluster persistence time increases with N, whereas the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel, to our knowledge, insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.
大多数细胞都具有运动能力。无论是单独行动还是集体行动，这使它们能够适应、重新排列并探索周围环境。迄今为止，对这种运动过程的生物物理特性的研究主要集中在两种极限情况上：一方面是单细胞的运动，另一方面是上皮等融合组织的动力学。作为介于两者之间的状态，由相对较少的细胞作为一个连贯的单元移动的小细胞簇受到的关注较少。然而，这种小的细胞簇在发育过程中以及癌症转移中都具有重要意义。在这项工作中，我们使用细胞 Potts 模型和分析活性物质理论来理解小细胞簇的运动如何随 N（簇中细胞的数量）而变化。建模和理论揭示了我们的两个主要发现：簇持续时间随 N 增加而增加，而本征扩散率随 N 降低。我们讨论了一些可以对更复杂的细胞簇的运动性质进行分析理解的环境，揭示了小尺度合作和细胞间对齐的聚焦效应可以克服多细胞簇的更大体积和内部无序性，从而提高整体迁移效率。我们展示了小簇集体趋硬性的这种增强，其迁移效率明显高于单细胞。我们的结果可能为我们所知的单细胞和大规模集体运动之间的联系提供了一些新的见解，并可能为小肿瘤细胞簇增强的转移潜力的生物物理起源指明方向。
