Gabuardi Thamara Liz, Lee Hyun Gyu, Lee Kyoung J
Department of Physics, Korea University, Seoul, Korea.
Sci Rep. 2022 Mar 9;12(1):3857. doi: 10.1038/s41598-022-07865-2.
Characteristics of cell migration in a confluent population depend on the nature of cell-to-cell interactions as well as cell-intrinsic properties such as the directional persistence in crawling. In addition, biological tissues (or cell cultures) almost always carry anisotropies and they too can significantly affect cell motility. In the light of this viewpoint, the emergence of cellular senescences in a confluent population of active cells raises an interesting question. Cellular senescence is a process through which a cell enters a permanent growth-arrest state and generally exhibits a dramatic body expansion. Therefore, randomly emerging senescent cells transform an initially homogeneous cell population to a "binary mixture" of two distinct cell types. Here, using in vitro cultures of MDA-MB-231 cells we investigate how spatially localized cellular senescence affect the motility of active cells within a confluent population. Importantly, we estimate the intercellular surface energy of the interface between non-senescent and senescent MDA-MB-231 cells by combining the analysis on the motile behaviors of non-senescent cells encircling senescent cells and the result of extensive numerical simulations of a cellular Potts model. We find that the adhesion of normal cells to senescent cells is much weaker than that among normal cells and that the 'arclength' traveled by a normal cell along the boundary of a senescent cell, on average, is several times greater than the persistence length of normal cell in a densely packed homogeneous population. The directional persistent time of normal cell during its contact with a senescent cell also increases significantly. We speculate that the phenomenon could be a general feature associated with senescent cells as the enormous expansion of senescent cell's membrane would inevitably decrease the density of cell adhesion molecules.
汇合细胞群体中的细胞迁移特征取决于细胞间相互作用的性质以及细胞内在特性，如爬行时的方向持久性。此外，生物组织（或细胞培养物）几乎总是具有各向异性，它们也会显著影响细胞运动。基于这一观点，活跃细胞汇合群体中细胞衰老的出现提出了一个有趣的问题。细胞衰老是一个细胞进入永久生长停滞状态并通常表现出显著体积增大的过程。因此，随机出现的衰老细胞将最初均匀的细胞群体转变为两种不同细胞类型的“二元混合物”。在这里，我们使用MDA - MB - 231细胞的体外培养来研究空间定位的细胞衰老如何影响汇合群体中活跃细胞的运动。重要的是，我们通过结合对围绕衰老细胞的非衰老细胞运动行为的分析以及细胞Potts模型的大量数值模拟结果，估算了非衰老和衰老MDA - MB - 231细胞之间界面的细胞间表面能。我们发现正常细胞与衰老细胞的黏附力比正常细胞之间的黏附力弱得多，并且正常细胞沿着衰老细胞边界平均“走过”的“弧长”比其在密集堆积的均匀群体中的持久长度大几倍。正常细胞与衰老细胞接触期间的方向持续时间也显著增加。我们推测这种现象可能是衰老细胞的一个普遍特征，因为衰老细胞膜的巨大扩张将不可避免地降低细胞黏附分子的密度。
