Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, Sorbonne Université, Paris, France.
Cell Biology and Cancer Unit, Institut Curie, PSL Research University, Sorbonne University, Paris, France.
Elife. 2022 Mar 18;11:e69229. doi: 10.7554/eLife.69229.
Migrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in (hTERT)-immortalizedRPE1 (retinal pigment epithelial) cells over long timescales. By live cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed toward protrusions with a 20-min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.
迁移细胞呈现出多种路径，从随机到高度定向。虽然随机运动可以用基础内在活动来解释，但持续的运动需要稳定的极化。在这里，我们定量研究了在长时程内（hTERT）永生化的 RPE1（视网膜色素上皮）细胞中持续迁移的出现。通过活细胞成像和动态微图案化，我们证明了核-高尔基体轴与迁移方向对齐，从而实现有效的细胞运动。我们表明，极化运输在突起方向上有 20 分钟的延迟，并且在破坏细胞内部组织后，迁移变得随机。最终，我们证明了局部光遗传学 Cdc42 激活可以使核-高尔基体轴定向。我们的工作表明，极化运输稳定了细胞的突起活性，而突起活性则使该极性轴定向，从而导致持续的细胞迁移。使用最小物理模型，我们表明这种反馈足以在数小时的时间尺度内再现细胞迁移的定量性质。
