Bio Interfaces, Leibniz Institute for New Materials, 66123 Saarbrücken, Germany.
Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):826-835. doi: 10.1073/pnas.1907845117. Epub 2019 Dec 27.
Dendritic cells "patrol" the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.
树突状细胞“巡逻”人体以检测病原体。在搜索过程中,树突状细胞通过变形虫样迁移进行随机游走。病原体检测的效率取决于随机游走的特性。目前尚不清楚树突状细胞如何控制这些特性。在这里,我们通过记录它们的长期轨迹,在明确定义的 2 维限制和 3 维胶原基质中量化树突状细胞的迁移。我们发现 2 种不同的迁移状态:持续迁移,在此期间,树突状细胞沿弯曲的路径移动,和扩散迁移,其特征是连续的急转弯。这些状态在肌动蛋白分布上表现出差异。我们的理论和实验分析表明,这种运动可以通过自发的肌动蛋白聚合波产生,这有助于树突状细胞的极化和迁移。持久和扩散迁移的相对分布可以通过改变分子肌动蛋白丝成核和组装速率来改变。因此,树突状细胞可以控制它们的迁移模式并适应特定的环境。我们的研究为树突状细胞如何调整其对病原体的搜索提供了一个新的视角。