Beijing National Laboratory for Condensed Matter Physics and Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
School of Systems Science and Institute of Nonequilibrium Systems, Beijing Normal University, Beijing, 100875, China.
Nat Commun. 2023 Aug 24;14(1):5166. doi: 10.1038/s41467-023-40858-x.
Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.
细胞迁移在许多生物过程中发挥着重要作用，但迁移细胞如何协调细胞内分子和亚细胞结构来调节其速度和方向尚不清楚。在这里，通过对鱼类角膜细胞内扩散和三维片状伪足结构的特征描述，我们观察到细胞内扩散与细胞迁移速度之间存在很强的正相关性，更重要的是，我们发现细胞迁移模式发生了转变，伴随着细胞内扩散的可逆变化和片状伪足结构的变形。与正常的快速模式不同，在新发现的缓慢模式中迁移的细胞具有变形的片状伪足，前端肿胀，后端变薄，细胞内扩散减少，片状伪足中的大分子呈分隔分布。此外，在转向细胞中，片状伪足结构和细胞内扩散动力学也发生了变化，左右对称性被打破。我们提出了一种机制，涉及到片状伪足中局部的肌动蛋白聚合和分子拥挤度的增加，以解释细胞如何在时空上协调细胞内扩散动力学和片状伪足结构来调节其迁移。
