Hong Lijun, Zhang Zhenquan, Wang Zihao, Yu Xiaochen, Zhang Jiajun
Guangdong Province Key Laboratory of Computational Science, <a href="https://ror.org/0064kty71">Sun Yat-sen University</a>, Guangzhou 510275, People's Republic of China and School of Mathematics, <a href="https://ror.org/0064kty71">Sun Yat-Sen University</a>, Guangzhou 510275, People's Republic of China.
Phys Rev E. 2024 Jun;109(6-1):064414. doi: 10.1103/PhysRevE.109.064414.
Phenotypic switching plays a crucial role in cell fate determination across various organisms. Recent experimental findings highlight the significance of protein compartmentalization via liquid-liquid phase separation in influencing such decisions. However, the precise mechanism through which phase separation regulates phenotypic switching remains elusive. To investigate this, we established a mathematical model that couples a phase separation process and a gene expression process with feedback. We used the chemical master equation theory and mean-field approximation to study the effects of phase separation on the gene expression products. We found that phase separation can cause bistability and bimodality. Furthermore, phase separation can control the bistable properties of the system, such as bifurcation points and bistable ranges. On the other hand, in stochastic dynamics, the droplet phase exhibits double peaks within a more extensive phase separation threshold range than the dilute phase, indicating the pivotal role of the droplet phase in cell fate decisions. These findings propose an alternative mechanism that influences cell fate decisions through the phase separation process. As phase separation is increasingly discovered in gene regulatory networks, related modeling research can help build biomolecular systems with desired properties and offer insights into explaining cell fate decisions.
表型转换在多种生物体的细胞命运决定中起着关键作用。最近的实验结果突出了通过液-液相分离实现的蛋白质区室化在影响此类决定方面的重要性。然而，相分离调节表型转换的精确机制仍然难以捉摸。为了研究这一点，我们建立了一个将相分离过程和具有反馈的基因表达过程相结合的数学模型。我们使用化学主方程理论和平均场近似来研究相分离对基因表达产物的影响。我们发现相分离会导致双稳态和双峰性。此外，相分离可以控制系统的双稳态特性，如分岔点和双稳态范围。另一方面，在随机动力学中，液滴相比稀相在更广泛的相分离阈值范围内表现出双峰，这表明液滴相在细胞命运决定中起关键作用。这些发现提出了一种通过相分离过程影响细胞命运决定的替代机制。随着在基因调控网络中越来越多地发现相分离，相关的建模研究可以帮助构建具有所需特性的生物分子系统，并为解释细胞命运决定提供见解。
