Sharma Yasha, Vargas Diego A, Pegoraro Adrian F, Lepzelter David, Weitz David A, Zaman Muhammad H
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
Integr Biol (Camb). 2015 Dec;7(12):1526-33. doi: 10.1039/c5ib00208g. Epub 2015 Nov 9.
Collective cell migration is ubiquitous in biology, from development to cancer; it occurs in complex systems comprised of heterogeneous cell types, signals and matrices, and requires large scale regulation in space and time. Understanding how cells achieve organized collective motility is crucial to addressing cellular and tissue function and disease progression. While current two-dimensional model systems recapitulate the dynamic properties of collective cell migration, quantitative three-dimensional equivalent model systems have proved elusive. To establish such a model system, we study cell collectives by tracking individuals within cell cohorts embedded in three dimensional collagen scaffolding. We develop a custom algorithm to quantify the temporal and spatial heterogeneity of motion in cell cohorts during motility events. In the absence of external driving agents, we show that these cohorts rotate in short bursts, <2 hours, and translate for up to 6 hours. We observe, track, and analyze three dimensional motion of cell cohorts composed of 3-31 cells, and pave a path toward understanding cell collectives in 3D as a complex emergent system.
集体细胞迁移在生物学中无处不在，从发育到癌症；它发生在由异质细胞类型、信号和基质组成的复杂系统中，并且需要在空间和时间上进行大规模调节。了解细胞如何实现有组织的集体运动对于理解细胞和组织功能以及疾病进展至关重要。虽然当前的二维模型系统概括了集体细胞迁移的动态特性，但定量三维等效模型系统却难以实现。为了建立这样一个模型系统，我们通过跟踪嵌入三维胶原蛋白支架中的细胞群体中的个体来研究细胞集体。我们开发了一种定制算法来量化运动事件期间细胞群体中运动的时间和空间异质性。在没有外部驱动因素的情况下，我们表明这些群体以短脉冲（<2小时）旋转，并平移长达6小时。我们观察、跟踪和分析由3-31个细胞组成的细胞群体的三维运动，并为将三维细胞集体理解为一个复杂的涌现系统铺平了道路。
