Anjum Sommer, Turner Llaran, Atieh Youmna, Eisenhoffer George T, Davidson Lance A
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Computational Modeling and Simulation Graduate Program, University of Pittsburgh, Pittsburgh, PA 15260, USA.
iScience. 2024 Sep 23;27(11):111017. doi: 10.1016/j.isci.2024.111017. eCollection 2024 Nov 15.
Homeostasis is necessary for epithelia to maintain barrier function and prevent the accumulation of defective cells. Unfit, excess, and dying cells in the larval zebrafish tail fin epidermis are removed via controlled cell death and extrusion. Extrusion coincides with oscillations of cell area, both in the extruding cell and its neighbors. Here, we develop a biophysical model of this process to explore the role of autonomous and non-autonomous mechanics. We vary biophysical properties and oscillatory behaviors of extruding cells and their neighbors along with tissue-wide cell density and viscosity. We find that cell autonomous processes are major contributors to the dynamics of extrusion, with the mechanical microenvironment providing a less pronounced contribution. We also find that some cells initially resist extrusion, influencing the duration of the expulsion process. Our model provides insights into the cellular dynamics and mechanics that promote elimination of unwanted cells from epithelia during homeostatic tissue maintenance.
内环境稳态对于上皮细胞维持屏障功能和防止缺陷细胞积累至关重要。斑马鱼幼鱼尾鳍表皮中不适合的、多余的和即将死亡的细胞通过可控的细胞死亡和挤出作用被清除。挤出过程与挤出细胞及其相邻细胞的细胞面积振荡同时发生。在这里，我们开发了一个该过程的生物物理模型，以探索自主和非自主力学的作用。我们改变挤出细胞及其相邻细胞的生物物理特性和振荡行为，以及组织范围内的细胞密度和粘度。我们发现细胞自主过程是挤出动力学的主要贡献因素，而机械微环境的贡献不太明显。我们还发现一些细胞最初会抵抗挤出，从而影响排出过程的持续时间。我们的模型为在稳态组织维持过程中促进上皮细胞中不需要的细胞清除的细胞动力学和力学提供了见解。
