Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration.
Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration.
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DOI：
10.7554/elife.83792
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发表时间：
2023-04-19
期刊：
影响因子：
7.7
通讯作者：
Maini PK
中科院分区：
文献类型：
--
作者：
Martinson WD;McLennan R;Teddy JM;McKinney MC;Davidson LA;Baker RE;Byrne HM;Kulesa PM;Maini PK
集体细胞迁移在脊椎动物发育中起着重要作用，但动态变化的微环境对这种现象的影响程度仍不清楚。在松散连接的神经嵴细胞（NCC）的迁移过程中的细胞外基质（ECM）组分纤连蛋白的分布的观察导致我们假设，NCC重塑最初点状ECM创建一个支架的尾随细胞，使他们能够形成强大的和连贯的流模式。我们评估这一想法在理论上的设置，开发一个基于个人的计算模型，结合了NCC和ECM之间的相互作用。ECM重塑、趋触性、接触引导和细胞-细胞排斥足以使细胞在计算机上建立流，然而，需要额外的机制，如趋化性，以始终引导细胞沿着正确的靶通道。进一步的模型研究表明，领导者和追随者细胞之间的接触指导和差分细胞-细胞排斥是通过防止流断裂来实现强大的集体细胞迁移的关键因素。全球敏感性分析和模拟增益和功能丧失实验表明，长距离迁移无干扰是最有可能发生时，领先的细胞专门创造ECM纤维，和尾随细胞专门响应环境的线索，通过上调机制，如接触指导。
Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loosely connected neural crest cells (NCCs) lead us to hypothesize that NCC remodeling of an initially punctate ECM creates a scaffold for trailing cells, enabling them to form robust and coherent stream patterns. We evaluate this idea in a theoretical setting by developing an individual-based computational model that incorporates reciprocal interactions between NCCs and their ECM. ECM remodeling, haptotaxis, contact guidance, and cell-cell repulsion are sufficient for cells to establish streams in silico, however, additional mechanisms, such as chemotaxis, are required to consistently guide cells along the correct target corridor. Further model investigations imply that contact guidance and differential cell-cell repulsion between leader and follower cells are key contributors to robust collective cell migration by preventing stream breakage. Global sensitivity analysis and simulated gain- and loss-of-function experiments suggest that long-distance migration without jamming is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance.
影响因子：
5.4
作者：
McKinney MC;McLennan R;Kulesa PM
通讯作者：
Kulesa PM
影响因子：
2.5
作者：
McLennan, Rebecca;Kulesa, Paul M.
通讯作者：
Kulesa, Paul M.
影响因子：
2
作者：
Wynn ML;Rupp P;Trainor PA;Schnell S;Kulesa PM
通讯作者：
Kulesa PM