Abstract:
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.
摘要:
细胞迁移在许多生物过程中起着重要作用,但是迁移细胞如何协调细胞内分子和亚细胞结构来调节它们的速度和方向仍然不清楚。这里,通过表征鱼角质细胞的细胞内扩散和三维层状结构,我们观察到细胞内扩散和细胞迁移速度之间的强正相关,更重要的是,发现具有可逆的细胞内扩散变化和层片结构变形的细胞迁移模式的切换。不同于正常的快速模式,在新发现的慢速模式中迁移的细胞具有变形的层状体,其前部肿胀,后部变薄,减少的细胞内扩散和分隔的大分子分布在lamellipodium中。此外,在转动细胞中,层片结构和细胞内扩散动力学也发生了变化,左右对称打破。我们提出了一种涉及前位肌动蛋白聚合和lamellipodium中分子拥挤增加的机制,以解释细胞如何时空协调细胞内扩散动力学和lamellipodium结构来调节其迁移。