A critical-like collective state leads to long-range cell communication in Dictyostelium discoideum aggregation.
A critical-like collective state leads to long-range cell communication in Dictyostelium discoideum aggregation.
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DOI：
10.1371/journal.pbio.1002602
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发表时间：
2017-04
期刊：
影响因子：
9.8
通讯作者：
Endres RG
中科院分区：
文献类型：
--
作者：
De Palo G;Yi D;Endres RG
从单细胞到多细胞行为的转变在早期发育中很重要，但很少研究。饥饿诱导的社会阿米巴Dictyosteelium discoideum聚集成多细胞蛞蝓是已知的，导致单细胞趋化性朝向发射脉冲的环磷酸腺苷（cAMP）。然而，在宏观尺度上，瞬时的短程化学梯度究竟是如何导致连贯的集体运动的？在这里，我们开发了一个多尺度模型，通过定量显微镜验证来描述从单个细胞的趋化性和兴奋性到数千个细胞的聚集的广泛行为。为了更好地理解长距离细胞间通讯的机制，从而聚集，我们分析了细胞间的相关性，显示了聚集开始时自组织的证据（而不是跟随领导细胞）。令人惊讶的是，细胞集体，尽管其有限的大小，显示已知的物理系统中的相变临界的功能。通过比较野生型和突变体细胞受损的聚集，我们发现最长的细胞间通信距离在野生型细胞，这表明临界提供了一个适应性的优势和最佳大小的聚集体的孢子的分散。多尺度模型和成像数据表明，细胞的黏菌Dictyosteelium discoideum最大限度地提高其细胞间的通信范围在聚合过程中的一个临界状态，从物理系统中的相变。细胞通常在细胞集合体中彼此偶联，例如早期发育期间的聚集体、发育生物体中的组织和疾病中的肿瘤。细胞如何在比典型的细胞间距离大得多的宏观距离上进行通信，以决定它们应该如何行为？在这里，我们开发了一个多尺度的社会阿米巴模型，从个体到数千个细胞的行为。我们发现，通过分泌的化学物质的局部细胞-细胞耦合可能会调整到一个临界值，导致紧急远程通信和提高灵敏度。因此，这些聚集体与细菌生物膜和神经元网络非常相似，都以脉冲方式进行通信。类似的组织原则也可能有助于我们理解癌症发展的显著稳健性。
The transition from single-cell to multicellular behavior is important in early development but rarely studied. The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate (cAMP). However, how exactly do transient, short-range chemical gradients lead to coherent collective movement at a macroscopic scale? Here, we developed a multiscale model verified by quantitative microscopy to describe behaviors ranging widely from chemotaxis and excitability of individual cells to aggregation of thousands of cells. To better understand the mechanism of long-range cell—cell communication and hence aggregation, we analyzed cell—cell correlations, showing evidence of self-organization at the onset of aggregation (as opposed to following a leader cell). Surprisingly, cell collectives, despite their finite size, show features of criticality known from phase transitions in physical systems. By comparing wild-type and mutant cells with impaired aggregation, we found the longest cell—cell communication distance in wild-type cells, suggesting that criticality provides an adaptive advantage and optimally sized aggregates for the dispersal of spores. A multiscale model and imaging data show that cells of the slime mold Dictyostelium discoideum maximize their cell—cell communication range during aggregation by a critical-like state known from phase transitions in physical systems. Cells are often coupled to each other in cell collectives, such as aggregates during early development, tissues in the developed organism, and tumors in disease. How do cells communicate over macroscopic distances much larger than the typical cell—cell distance to decide how they should behave? Here, we developed a multiscale model of social amoeba, spanning behavior from individuals to thousands of cells. We show that local cell—cell coupling via secreted chemicals may be tuned to a critical value, resulting in emergent long-range communication and heightened sensitivity. Hence, these aggregates are remarkably similar to bacterial biofilms and neuronal networks, all communicating in a pulselike fashion. Similar organizing principles may also aid our understanding of the remarkable robustness in cancer development.