Chen Yixuan, Guan Guoye, Tang Lei-Han, Tang Chao
South Bay Interdisciplinary Science Center, Songshan Lake Materials Laboratory, Dongguan, China.
Department of Physics, Sichuan University, Chengdu, China.
Elife. 2025 Jul 22;13:RP96421. doi: 10.7554/eLife.96421.
Cell polarization is a critical process that separates molecular species into two distinct regions in prokaryotic and eukaryotic cells, guiding biological processes such as cell division and cell differentiation. Although several underlying antagonistic reaction-diffusion networks capable of setting up cell polarization have been identified experimentally and theoretically, our understanding of how to manipulate pattern stability and asymmetry remains incomplete, especially when only a subset of network components is known. Here, we present numerical results to show that the polarized pattern of an antagonistic 2-node network collapses into a homogeneous state when subjected to single-sided self-regulation, single-sided additional regulation, or unequal system parameters. However, polarity restoration can be achieved by combining two modifications with opposing effects. Additionally, spatially inhomogeneous parameters favoring respective domains stabilize their interface at designated locations. To connect our findings to cell polarity studies of the nematode zygote, we reconstituted a 5-node network where a 4-node circuit with full mutual inhibitions between anterior and posterior is modified by a mutual activation in the anterior and an additional mutual inhibition between the anterior and posterior. Once again, a generic set of kinetic parameters moves the interface towards either the anterior or posterior end, yet a polarized pattern can be stabilized through tuning of one or more parameters coupled to intracellular or extracellular spatial cues. A user-friendly software, , is constructed to facilitate the exploration of networks with alternative node numbers, parameter values, and regulatory pathways.
细胞极化是一个关键过程,它将分子种类在原核细胞和真核细胞中分隔到两个不同区域,引导诸如细胞分裂和细胞分化等生物学过程。尽管已经通过实验和理论鉴定出了几种能够建立细胞极化的潜在拮抗反应扩散网络,但我们对如何操纵模式稳定性和不对称性的理解仍然不完整,尤其是当仅知道网络组件的一个子集时。在这里,我们给出数值结果表明,当受到单侧自我调节、单侧额外调节或系统参数不相等时,拮抗双节点网络的极化模式会坍缩为均匀状态。然而,通过结合具有相反作用的两种修改可以实现极性恢复。此外,有利于各自区域的空间不均匀参数会在指定位置稳定它们的界面。为了将我们的发现与线虫受精卵的细胞极性研究联系起来,我们重建了一个五节点网络,其中一个在前部和后部之间具有完全相互抑制的四节点回路通过前部的相互激活和前部与后部之间的额外相互抑制进行了修改。同样,一组通用的动力学参数会使界面朝着前端或后端移动,然而,通过调整与细胞内或细胞外空间线索相关的一个或多个参数,可以稳定极化模式。构建了一个用户友好的软件 ,以促进对具有替代节点数、参数值和调节途径的网络的探索。