Center for Systems Biology Dresden, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Soft Matter. 2022 Oct 19;18(40):7877-7886. doi: 10.1039/d2sm00757f.
Coordinated and cooperative motion of cells is essential for embryonic development, tissue morphogenesis, wound healing and cancer invasion. A predictive understanding of the emergent mechanical behaviors in collective cell motion is challenging due to the complex interplay between cell-cell interactions, cell-matrix adhesions and active cell behaviors. To overcome this challenge, we develop a predictive cellular vertex model that can delineate the relative roles of substrate rigidity, tissue mechanics and active cell properties on the movement of cell collectives. We apply the model to the specific case of collective motion in cell aggregates as they spread into a two-dimensional cell monolayer adherent to a soft elastic matrix. Consistent with recent experiments, we find that substrate stiffness regulates the driving forces for the spreading of cellular monolayer, which can be pressure-driven or crawling-based depending on substrate rigidity. On soft substrates, cell monolayer spreading is driven by an active pressure due to the influx of cells coming from the aggregate, whereas on stiff substrates, cell spreading is driven primarily by active crawling forces. Our model predicts that cooperation of cell crawling and tissue pressure drives faster spreading, while the spreading rate is sensitive to the mechanical properties of the tissue. We find that solid tissues spread faster on stiff substrates, with spreading rate increasing with tissue tension. By contrast, the spreading of fluid tissues is independent of substrate stiffness and is slower than solid tissues. We compare our theoretical results with experimental results on traction force generation and spreading kinetics of cell monolayers, and provide new predictions on the role of tissue fluidity and substrate rigidity on collective cell motion.
细胞的协调和合作运动对于胚胎发育、组织形态发生、伤口愈合和癌症侵袭至关重要。由于细胞间相互作用、细胞-基质黏附以及活跃的细胞行为之间的复杂相互作用，对集体细胞运动中出现的机械行为进行预测性理解具有挑战性。为了克服这一挑战，我们开发了一种预测性细胞顶点模型，可以描绘基质刚性、组织力学和活跃细胞特性对细胞集体运动的相对作用。我们将该模型应用于细胞聚集体在软弹性基质上二维细胞单层中扩散的具体情况。与最近的实验一致，我们发现基底刚性调节细胞单层扩散的驱动力，这可以是压力驱动的，也可以是基于爬行的，具体取决于基底的刚性。在软基底上，由于来自聚集体的细胞流入，细胞单层的扩散是由主动压力驱动的，而在硬基底上，细胞的扩散主要是由主动爬行力驱动的。我们的模型预测，细胞爬行和组织压力的协同作用可以驱动更快的扩散，而扩散速度对组织力学性质敏感。我们发现，刚性组织在硬基底上扩散得更快，扩散速度随组织张力的增加而增加。相比之下，流体组织的扩散与基底刚性无关，且比刚性组织慢。我们将理论结果与细胞单层牵引力生成和扩散动力学的实验结果进行比较，并对组织流动性和基底刚性对集体细胞运动的作用提供新的预测。
