To lead or to herd: optimal strategies for 3D collective migration of cell clusters
To lead or to herd: optimal strategies for 3D collective migration of cell clusters
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DOI：
10.1007/s10237-020-01290-y
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发表时间：
2020-01-29
影响因子：
3.5
通讯作者：
Katira, Parag
中科院分区：
文献类型：
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作者：
Collins, Tyler A.;Yeoman, Benjamin M.;Katira, Parag
成簇迁移的细胞在许多生物学过程中发挥重要作用，例如胚胎发生、伤口愈合和癌症进展期间的肿瘤转移。各种环境和生化因素可以影响具有不同程度的细胞自主性和细胞间耦合强度的细胞的集体迁移。例如，弱耦合的细胞可以在来自相邻细胞或环境的接触引导的影响下集体移动。或者，强耦合的细胞可以跟随一个或多个领导细胞作为单个内聚单元移动。此外，这些细胞之间的化学和机械信号可能会改变耦合的程度，并确定有效的集群大小。能够理解这种集体细胞迁移过程对于预测和操纵关键生物过程的结果至关重要。在这里，我们专注于了解各种环境和细胞因素如何影响小细胞群在3D纤维基质内集体迁移。我们结合联合收割机现有的知识，单细胞迁移在2D和3D环境中，以前的实验观察细胞间的相互作用和集体迁移，和一个新开发的随机模型的细胞迁移在3D矩阵，模拟迁移的细胞簇在不同的生理相关的环境。我们的研究结果表明，基于细胞外环境和细胞-细胞机械耦合的强度，出现了两种不同的最佳方法来驱动集体细胞迁移。有效地采用这两种不同的迁移策略的能力对于细胞集体迁移通过体内的异质组织环境可能是至关重要的。
Cells migrating in clusters play a significant role in a number of biological processes such as embryogenesis, wound healing, and tumor metastasis during cancer progression. A variety of environmental and biochemical factors can influence the collective migration of cells with differing degrees of cell autonomy and inter-cellular coupling strength. For example, weakly coupled cells can move collectively under the influence of contact guidance from neighboring cells or the environment. Alternatively strongly coupled cells might follow one or more leader cells to move as a single cohesive unit. Additionally, chemical and mechanical signaling between these cells may alter the degree of coupling and determine effective cluster sizes. Being able to understand this collective cell migration process is critical in the prediction and manipulation of outcomes of key biological processes. Here we focus on understanding how various environmental and cellular factors influence small clusters of cells migrating collectively within a 3D fibrous matrix. We combine existing knowledge of single-cell migration in 2D and 3D environments, prior experimental observations of cell-cell interactions and collective migration, and a newly developed stochastic model of cell migration in 3D matrices, to simulate the migration of cell clusters in different physiologically relevant environments. Our results show that based on the extracellular environment and the strength of cell-cell mechanical coupling, two distinct optimal approaches to driving collective cell migration emerge. The ability to effectively employ these two distinct migration strategies might be critical for cells to collectively migrate through the heterogeneous tissue environments within the body.