上皮细胞集体迁移过程中的密度波动和边界力直接影响前导细胞的可塑性
Density fluctuations and border forces direct leader cell plasticity during collective epithelial migrations
摘要：
上皮细胞单层通过在单层边界形成由前导细胞产生的指状突起而在基底上扩张。凝聚集体中个体之间的信息传递和交流导致长程序、涡旋结构和无序到有序的相变。我们提出以下问题：什么是领导者？追随者在领导细胞形成中的作用是什么？我们使用基于粒子的模型来模拟上皮细胞在9.4 kPa、21 kPa和33 kPa硬度的基底上的迁移。系综中细胞运动的动力学由取向Vicsek和相邻粒子之间的细胞间相互作用决定。该模型还包括弯曲，曲率为基础的运动，和肌动蛋白收缩电缆的轮廓上的力量，除了密度依赖性噪声和细胞增殖。我们发现，边界部队是必不可少的领导细胞的形成和基板上的上皮单层的整体面积扩张。单层的径向速度和面积扩张同意不同刚度的基板上的上皮细胞的实验报告。在单层的特定区域内的追随者细胞中的排序在较高刚度的基底上是明显的，并且在领导细胞出现之前发生。我们表明，细胞密度增加的区域发生在所有三种基板上的领导细胞边缘的后面。最后，我们评估的作用，细胞分裂的速度在单层的顺序。这些结果表明，单层异质性，在内部区域的密度不稳定性所造成的，与上皮细胞迁移过程中的领导细胞的形成。
英文摘要：
Epithelial cell monolayers expand on substrates by forming finger-like protrusions, created by leader cells, in the monolayer boundary. Information transmission and communication between individual entities in the cohesive collective lead to long-range order, vortical structures, and disorder to ordered phase transitions. We ask the following questions: what makes a leader? What is the role of followers in leader cell formation? We used a particle-based model to simulate epithelial cell migrations on substrates of 9.4 kPa, 21 kPa and 33 kPa stiffness. The dynamics of cellular motion in the ensemble are governed by orientational Vicsek and inter-cellular interactions between neighboring particles. The model also includes bending, curvature-based motility, and acto-myosin contractile cable forces on the contour, in addition to density dependent noise and cell proliferations. We show that border forces are essential in the leader cell formation and the overall areal expansions of epithelial monolayers on substrates. Radial velocities and areal expansions of the monolayer agree with experiments reported for epithelial cells on substrates of varied stiffness. Ordering in follower cells within a specific region of the monolayer was apparent on substrates of higher stiffness and occurred prior to the emergence of leader cells. We demonstrate that regions of increased cell density occur behind the leader cell edge on all three substrates. Finally, we assessed the role of cell divisions on the ordering of velocities in the monolayer. These results demonstrate that monolayer heterogeneities, caused by density instabilities in the interior regions, correlate with leader cell formation during epithelial migrations.
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