Mathematical model results for: Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration

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 agent-based 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 investigations of the model 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 underexpression/overexpression 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. This dataset contains summary statistics, movies, parameter values, and photos obtained from individual realizations of the mathematical model.

集体细胞迁移（Collective cell migration）在脊椎动物发育过程中扮演着至关重要的角色，然而动态变化的微环境对这一现象的影响程度仍有待阐明。针对松散连接的神经嵴细胞（neural crest cells, NCCs）迁移过程中细胞外基质（extracellular matrix, ECM）组分纤连蛋白（fibronectin）的分布观测，促使我们提出假说：神经嵴细胞对初始呈点状分布的细胞外基质进行重塑，可为尾随细胞搭建支撑骨架，使其能够形成稳定且连贯的迁移流模式。我们通过构建纳入神经嵴细胞与其细胞外基质之间双向相互作用的基于代理的模型，在理论框架下对这一假说展开验证。研究发现，细胞外基质重塑、趋硬性（haptotaxis）、接触导向（contact guidance）以及细胞间排斥作用，足以让细胞在计算机模拟（in silico）中形成迁移流；但若要使细胞始终沿正确的目标通路迁移，则需要引入趋化性（chemotaxis）等额外机制。对该模型的进一步研究表明，接触导向以及领头细胞与尾随细胞间的差异性细胞间排斥作用，可通过阻止迁移流断裂，成为实现稳定集体细胞迁移的关键因素。全局敏感性分析与模拟的基因过表达/低表达实验结果显示，当领头细胞专门负责构建细胞外基质纤维，而尾随细胞通过上调接触导向等机制以响应环境信号时，最有可能实现无拥堵的长距离细胞迁移。本数据集包含从该数学模型的各独立模拟实例中获取的汇总统计数据、影像、参数取值与图像。