标题： Eph-ephrin介导的差异持续性作为细胞分选的机制 显示英文标题

标题： Eph-ephrin-mediated differential persistence as a mechanism for cell sorting

摘要： 细胞分选/分离现象，即细胞在空间上组织成特定细胞类型或功能的簇，对于组织形态发生是必不可少的。 这种自组织过程涉及机械、生化和细胞机制之间的相互作用，这些机制在各种空间和时间尺度上起作用。 已经提出了几种细胞分选机制；然而，这些机制的物理性质以及它们如何导致对称或不对称的细胞分选仍然不清楚。 在这里，我们使用基因修饰的人胚胎肾（HEK293）细胞共培养的实验数据和数值模拟，展示了基于细胞运动持续性暂时增加的细胞分选机制的存在。 该机制在细胞过表达与eprinB1相关的受体EphB2后，与其过表达eprinB1的细胞相互作用时被激活。 我们证明该机制足以引起细胞分选，打破分选动力学的对称性，并表明这种短暂的差异持续状态的持续时间对于增强分选是最优的。 此外，我们证明当与其他相互作用机制结合时，例如方向变化——也称为运动抑制的接触——和粘附力，差异持续性显著缩短了分选的时间尺度。 我们的研究结果为细胞混合物的行为、非互惠相互作用的相关性提供了见解，并可能为发育过程和组织图案形成提供见解。 显示英文摘要

摘要： The phenomenon of cell sorting/segregation, by which cells organise spatially into clusters of specific cell type or function, is essential for tissue morphogenesis. This self-organization process involves an interplay between mechanical, biochemical, and cellular mechanisms that act across various spatial and temporal scales. Several mechanisms for cell sorting have been proposed; however, the physical nature of these mechanisms and how they lead to symmetric or asymmetric cell sorting remains unclear. Here, using experimental data from cocultures of genetically modified Human Embryonic Kidney (HEK293) cells and numerical simulations, we show the existence of a cell sorting mechanism based on transient increases in the persistence of motion of cells. This mechanism is activated on cells overexpressing the ephrinB1-related receptor EphB2 after their interaction with cells overexpressing ephrinB1. We show that this mechanism is sufficient to cause cell sorting, breaking the symmetry of the sorting dynamics, and show that the duration of this transient differential persistence state is optimal for enhancing sorting. Furthermore, we show that in combination with other interaction mechanisms, such as changes in direction-also known as contact inhibition of locomotion-and adhesion forces, differential persistence significantly reduces the timescale of sorting. Our findings offer insights into the behaviour of cell mixtures, the relevance of non-reciprocal interactions, and may provide insight into developmental processes and tissue patterning.