基于信号分子双向输运的运动细胞极性反转模拟

冯世亮; 朱卫平

doi:10.6052/0459-1879-14-242

基于信号分子双向输运的运动细胞极性反转模拟

冯世亮,
朱卫平^,

上海大学, 上海市应用数学和力学研究所, 上海200072

基金项目: 国家自然科学基金资助项目(31370940).

详细信息

通讯作者:
朱卫平,教授,主要研究方向:固体力学,细胞生物力学.E-mail:wpzhu@shu.edu.cn

中图分类号: Q615
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出版历程
- 收稿日期: 2014-08-17
- 修回日期: 2014-10-30
- 刊出日期: 2015-03-17

SIMULATION FOR REVERSAL OF CELL POLARITY BASED ON BIDIRECTIONAL TRANSPORT OF SIGNALING MOLECULES

Feng Shiliang,
Zhu Weiping^,

Shanghai University, Shanghai Institute of Applied Mathematics and Mechanics, Shanghai 200072, China

Funds: The project was supported by the National Natural Science Foundation of China (31370940).

摘要

摘要: 为解释运动细胞极性反转实验所发生的现象, 依据调控细胞极化的信号级联转导关系, 构建了包含一对非稳态二维反应—扩散方程的数学模型, 并采用格子Boltzmann 方法数值求解. 数值实验显示, 当反向信号使胞内Rac 的活化梯度值达到和超过初始正向极化梯度的1.5 倍时, 负责细胞极化的Rac-PIs 反馈回路产生时空调控效应, 可驱动伪足标识信号分子(如磷酸激酶(PI3K) 和磷脂酰肌醇-3, 4, 5- 三磷酸(PIP₃)) 和尾部标识信号分子(如磷酸酶(PTEN) 和磷脂酰肌醇-4, 5- 双磷酸(PIP₂)) 发生双向输运, 并最终重新积聚于对极. 模拟得到的极性反转时程曲线与已有实验吻合. 此外, 针对实验观测到的新伪足开始形成与原先伪足完全消失之间存在着延滞时间(~30 s), 该文证实这是由于细胞两极对游离态激活酶(例如, PI3K) 展开竞争所致, 无需引入前人所设想的全局性抑制因子的作用.
- 运动细胞 /
- 极性反转 /
- 细胞骨架 /
- 信号转导 /
- 数学模型
Abstract: To investigate the mechanisms underlying the reversal of cell polarity, a mathematical model consisting of a pair of reaction-di usion equations was presented and solved numerically with the Lattice—Boltzmann method. It was found that, by applying a reversal gradient of Rac signal in a cell, labels for lamellipod (i.e., PI3K, and PIP₃) would disappear from the front of cell, and redistribute to the rear, while labels for tail (i.e., PTEN, PIP₂) would act oppositely. The spatiotemporal patterns of lamellipod and tail interconversion derived from our numerical simulation agreed well with that of the experimental observations. Besides, the time delay taking place between actin assembly at the new front and disassembly at the previous front was medicated by the completion of an activator (i.e., PI3K), without the help of a supposed "global inhibitor".
- motile cells /
- repolarization /
- cytoskeleton /
- signaling transduction /
- mathematical model

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