极性(国际关系)
双稳态
生物系统
电池极性
颂歌
反应扩散系统
物理
统计物理学
非正面反馈
常微分方程
正面反馈
计算机科学
微分方程
化学
数学
数学分析
细胞
生物
量子力学
生物化学
工程类
电压
电气工程
作者
Siarhei Hladyshau,Kaiyun Guan,Nivedita Nivedita,Beverly Errede,Denis Tsygankov,Timothy C. Elston
出处
期刊:Cells
[MDPI AG]
日期:2024-08-15
卷期号:13 (16): 1358-1358
标识
DOI:10.3390/cells13161358
摘要
Cell polarity refers to the asymmetric distribution of proteins and other molecules along a specified axis within a cell. Polarity establishment is the first step in many cellular processes. For example, directed growth or migration requires the formation of a cell front and back. In many cases, polarity occurs in the absence of spatial cues. That is, the cell undergoes symmetry breaking. Understanding the molecular mechanisms that allow cells to break symmetry and polarize requires computational models that span multiple spatial and temporal scales. Here, we apply a multiscale modeling approach to examine the polarity circuit of yeast. In addition to symmetry breaking, experiments revealed two key features of the yeast polarity circuit: bistability and rapid dismantling of the polarity site following a loss of signal. We used modeling based on ordinary differential equations (ODEs) to investigate mechanisms that generate these behaviors. Our analysis revealed that a model involving positive and negative feedback acting on different time scales captured both features. We then extend our ODE model into a coarse-grained reaction–diffusion equation (RDE) model to capture the spatial profiles of polarity factors. After establishing that the coarse-grained RDE model qualitatively captures key features of the polarity circuit, we expand it to more accurately capture the biochemical reactions involved in the system. We convert the expanded model to a particle-based model that resolves individual molecules and captures fluctuations that arise from the stochastic nature of biochemical reactions. Our models assume that negative regulation results from negative feedback. However, experimental observations do not rule out the possibility that negative regulation occurs through an incoherent feedforward loop. Therefore, we conclude by using our RDE model to suggest how negative feedback might be distinguished from incoherent feedforward regulation.
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