Department of Physics and BioInspired Syracuse, Syracuse University, Syracuse, New York.
Department of Physics and BioInspired Syracuse, Syracuse University, Syracuse, New York.
Biophys J. 2022 Dec 6;121(23):4624-4634. doi: 10.1016/j.bpj.2022.10.029. Epub 2022 Oct 25.
Collective chemotaxis, where single cells cannot climb a biochemical signaling gradient but clusters of cells can, has been observed in different biological contexts, including confluent tissues where there are no gaps or overlaps between cells. Although particle-based models have been developed that predict important features of collective chemotaxis, the mechanisms in those models depend on particle overlaps, and so it remains unclear if they can explain behavior in confluent systems. Here, we develop an open-source code that couples a two-dimensional Voronoi simulation for confluent cell mechanics to a dynamic chemical signal that can diffuse, advect, and/or degrade and use the code to study potential mechanisms for collective chemotaxis in cellular monolayers. We first study the impact of advection on collective chemotaxis and delineate a regime where advective terms are important. Next, we investigate two possible chemotactic mechanisms, contact inhibition of locomotion and heterotypic interfacial tension, and demonstrate that both can drive collective chemotaxis in certain parameter regimes. We further demonstrate that the scaling behavior of cluster motion is well captured by simple analytic theories.
群体趋化性,即单个细胞无法爬上生化信号梯度,但细胞簇可以,这种现象在不同的生物学背景下都有观察到,包括细胞之间没有间隙或重叠的融合组织。尽管已经开发出基于粒子的模型来预测群体趋化性的重要特征,但这些模型中的机制依赖于粒子重叠,因此仍然不清楚它们是否可以解释融合系统中的行为。在这里,我们开发了一个开源代码,将用于融合细胞力学的二维 Voronoi 模拟与可以扩散、对流和/或降解的动态化学信号耦合起来,并使用该代码研究细胞单层中群体趋化性的潜在机制。我们首先研究了对流对群体趋化性的影响,并划定了一个对流项很重要的区域。接下来,我们研究了两种可能的趋化机制,即运动接触抑制和异型界面张力,并证明这两种机制都可以在某些参数区域驱动群体趋化性。我们进一步证明了簇运动的标度行为可以很好地用简单的解析理论来描述。