基于信号分子双向输运的运动细胞极性反转模拟

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. 

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

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".