Belotti Yuri, McGloin David, Weijer Cornelis J
School of Science and Engineering, University of Dundee, Dundee, Scotland, UK.
School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Commun Integr Biol. 2021 Jan 28;14(1):5-14. doi: 10.1080/19420889.2021.1872917.
Migratory environments of various eukaryotic cells, such as amoeba, leukocytes and cancer cells, typically involve spatial confinement. Numerous studies have recently emerged, aimed to develop experimental platforms that better recapitulate the characteristics of the cellular microenvironment. Using microfluidic technologies, we show that increasing confinement of Dictyostelium discoideum cells into narrower micro-channels resulted in a significant change in the mode of migration and associated arrangement of the actomyosin cytoskeleton. We observed that cells tended to migrate at constant speed, the magnitude of which was dependent on the size of the channels, as was the locomotory strategy adopted by each cell. Two different migration modes were observed, pseudopod-based and bleb-based migration, with bleb based migration being more frequent with increasing confinement and leading to slower migration. Beside the migration mode, we found that the major determinants of cell speed are its protrusion rate, the amount of F-actin at its leading edge and the number of actin foci. Our results highlighted the impact of the microenvironments on cell behavior. Furthermore, we developed a novel quantitative movement analysis platform for mono-dimensional cell migration that allows for standardization and simplification of the experimental conditions and aids investigation of the complex and dynamic processes occurring at the single-cell level.
各种真核细胞的迁移环境,如变形虫、白细胞和癌细胞,通常涉及空间限制。最近出现了大量研究,旨在开发能更好地重现细胞微环境特征的实验平台。利用微流控技术,我们发现将盘基网柄菌细胞限制在更窄的微通道中会导致迁移模式和肌动球蛋白细胞骨架相关排列的显著变化。我们观察到细胞倾向于以恒定速度迁移,其大小取决于通道尺寸,每个细胞采用的运动策略也是如此。观察到两种不同的迁移模式,基于伪足的迁移和基于气泡的迁移,随着限制增加,基于气泡的迁移更频繁且导致迁移速度变慢。除了迁移模式,我们发现细胞速度的主要决定因素是其突出率、前沿的F - 肌动蛋白量和肌动蛋白焦点数量。我们的结果突出了微环境对细胞行为的影响。此外,我们开发了一种用于一维细胞迁移的新型定量运动分析平台,该平台可实现实验条件的标准化和简化,并有助于研究单细胞水平上发生的复杂动态过程。