Modeling and measuring signal relay in noisy directed migration of cell groups.
Modeling and measuring signal relay in noisy directed migration of cell groups.
复制标题
DOI：
10.1371/journal.pcbi.1003041
复制
发表时间：
2013
影响因子：
4.3
通讯作者：
Losert W
中科院分区：
文献类型：
--
作者：
Guven C;Rericha E;Ott E;Losert W
我们建立了一个粗粒度的随机模型来研究信号传递对盘基网柄菌迁移细胞集体行为的影响。在实验中，细胞表现出一系列的集体迁移模式，包括不相关的运动，部分局部流的形成，以及聚集，这取决于细胞的类型和信号分子环磷酸腺苷(CAMP)的外部线性浓度梯度的强度。从我们的模型中我们发现，细胞的cAMP分泌速率和梯度腔内cAMP的降解率这两个过程的竞争可以定量地描述细胞的迁移模式。对于外部线性梯度信号的大范围强度，模型模拟与实验进行了比较。有了降解，模型分泌细胞形成了流，并有效地横过了梯度，但在没有降解的情况下，我们发现模型分泌细胞形成了团块，没有流。这表明，观测到的河流中有效的集体迁移不仅需要信号的传递，而且还需要信号的退化。此外，我们的模型允许我们检测和量化相关运动的前体，即使在细胞没有表现出明显的流动时也是如此。在包括血管生成、原肠形成、子实体形成和伤口愈合在内的各种生物过程中，观察到集体细胞的迁移。例如，盘基藻在其集体运动的早期阶段表现出高度动态的模式，如溪流和丛生生物，并已成为研究集体迁徙的模式生物。在这项研究中，我们开发了一个概念性的、最小的、计算模型来分析导致集体模式出现的动态过程以及与外部注入cAMP信号、细胞间cAMP分泌速率和cAMP降解率相关的依赖。我们证明了退化对于再现实验观察到的集体迁移模式是必要的，并展示了我们的模型如何可以用来揭示迁移模式对细胞特性的基本依赖关系。我们的数值观测阐明了不同可能的运动类型，并量化了集体运动的开始。因此，该模型允许我们区分由外部信号引导的噪声运动和弱相关运动。
We develop a coarse-grained stochastic model for the influence of signal relay on the collective behavior of migrating Dictyostelium discoideum cells. In the experiment, cells display a range of collective migration patterns, including uncorrelated motion, formation of partially localized streams, and clumping, depending on the type of cell and the strength of the external, linear concentration gradient of the signaling molecule cyclic adenosine monophosphate (cAMP). From our model, we find that the pattern of migration can be quantitatively described by the competition of two processes, the secretion rate of cAMP by the cells and the degradation rate of cAMP in the gradient chamber. Model simulations are compared to experiments for a wide range of strengths of an external linear-gradient signal. With degradation, the model secreting cells form streams and efficiently transverse the gradient, but without degradation, we find that model secreting cells form clumps without streaming. This indicates that the observed effective collective migration in streams requires not only signal relay but also degradation of the signal. In addition, our model allows us to detect and quantify precursors of correlated motion, even when cells do not exhibit obvious streaming. Collective cell migration is observed in various biological processes including angiogenesis, gastrulation, fruiting body formation, and wound healing. Dictyostelium discoideum, for example, exhibits highly dynamic patterns such as streams and clumps during its early phases of collective motion and has served as a model organism for the study of collective migration. In this study, facilitated by experiments, we develop a conceptual, minimalistic, computational model to analyze the dynamical processes leading to the emergence of collective patterns and the associated dependence on the external injection of a cAMP signal, the intercellular cAMP secretion rate, and the cAMP degradation rate. We demonstrate that degradation is necessary to reproduce the experimentally observed collective migration patterns, and show how our model can be utilized to uncover basic dependences of migration modes on cell characteristics. Our numerical observations elucidate the different possible types of motion and quantify the onset of collective motion. Thus, the model allows us to distinguish noisy motion guided by the external signal from weakly correlated motion.
登录
查看更多内容
DOI：
10.1088/0305-4470/30/5/009
发表时间：
1997-03-07
期刊：
JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL
影响因子：
--
作者：
Czirok, A;Stanley, HE;Vicsek, T
通讯作者：
Vicsek, T
影响因子：
7.8
作者：
DEVREOTES, PN;DERSTINE, PL;STECK, TL
通讯作者：
STECK, TL
影响因子：
3.4
作者：
GAIL, MH;BOONE, CW
通讯作者：
BOONE, CW
影响因子：
21.3
作者：
Andrew, Natalie;Insall, Robert H.
通讯作者：
Insall, Robert H.
影响因子：
2
作者：
Campos, Daniel;Mendez, Vicenc;Llopis, Isaac
通讯作者：
Llopis, Isaac