George Alexander, Akhavan Naghmeh, Peercy Bradford E, Starz-Gaiano Michelle
Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Department of Mathematics and Statistics, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
iScience. 2025 Feb 5;28(3):111959. doi: 10.1016/j.isci.2025.111959. eCollection 2025 Mar 21.
Migratory cells respond to graded concentrations of diffusible chemoattractants , but how complex tissue geometries impact chemotaxis is poorly understood. To address this, we studied the Drosophila border cells. Live-imaged border cells varied in their chemotactic migration speeds, which correlated positionally with distinct architectures. We then developed a reduced mathematical model to determine how chemoattractant distribution is affected by tissue architecture. Larger extracellular volumes locally dampened the chemoattractant gradient and, when coupled with an agent-based motion of the cluster, reduced cell speeds. This suggests that chemoattractant levels vary by tissue architectures, informing cell migration behaviors locally, which we tested Genetically elevating chemoattractant levels slowed migration in specific architectural regions, while mutants with spacious tissue structure rescued defects from high chemoattractant levels, promoting punctual migration. Our results highlight the interplay between tissue geometry and the local distribution of signaling molecules to orchestrate cell migration.
迁移细胞对可扩散趋化因子的梯度浓度作出反应，但复杂的组织几何结构如何影响趋化作用却知之甚少。为了解决这个问题，我们研究了果蝇的边界细胞。实时成像的边界细胞在趋化迁移速度上各不相同，这与不同的结构在位置上相关。然后，我们开发了一个简化的数学模型，以确定组织结构如何影响趋化因子的分布。更大的细胞外体积会局部减弱趋化因子梯度，并且当与细胞簇的基于智能体的运动相结合时，会降低细胞速度。这表明趋化因子水平因组织结构而异，在局部为细胞迁移行为提供信息，我们对此进行了测试。通过基因手段提高趋化因子水平会减缓特定结构区域的迁移，而具有宽敞组织结构的突变体则能挽救高趋化因子水平导致的缺陷，促进准时迁移。我们的结果突出了组织几何结构与信号分子局部分布之间的相互作用，以协调细胞迁移。
