Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Institut Curie, UMR144, CNRS, PSL University, Paris, France.
Dev Cell. 2024 Sep 23;59(18):2414-2428.e8. doi: 10.1016/j.devcel.2024.05.024. Epub 2024 Jun 12.
In crowded microenvironments, migrating cells must find or make a path. Amoeboid cells are thought to find a path by deforming their bodies to squeeze through tight spaces. Yet, some amoeboid cells seem to maintain a near-spherical morphology as they move. To examine how they do so, we visualized amoeboid human melanoma cells in dense environments and found that they carve tunnels via bleb-driven degradation of extracellular matrix components without the need for proteolytic degradation. Interactions between adhesions and collagen at the cell front induce a signaling cascade that promotes bleb enlargement via branched actin polymerization. Large blebs abrade collagen, creating feedback between extracellular matrix structure, cell morphology, and polarization that enables both path generation and persistent movement.
在拥挤的微观环境中，迁移细胞必须找到或开辟一条路径。人们认为变形虫细胞通过改变身体形状来挤压穿过狭小的空间来找到一条路径。然而，有些变形虫细胞在移动时似乎保持着近乎球形的形态。为了研究它们是如何做到这一点的，我们在密集的环境中可视化了变形虫状的人类黑色素瘤细胞，发现它们通过泡状突起驱动的细胞外基质成分降解来挖掘隧道，而不需要蛋白水解降解。细胞前缘的黏附和胶原之间的相互作用诱导了一个信号级联反应，通过分支的肌动蛋白聚合促进泡状突起的扩大。大的泡状突起会磨损胶原蛋白，从而在细胞外基质结构、细胞形态和极化之间产生反馈，使路径生成和持续运动成为可能。
