细胞运动和分裂的皮层因子反馈模型
Cortical Factor Feedback Model for Cellular Locomotion and Cytofission
摘要：
真核细胞可以在不受外部信号引导的情况下自发运动。对于这种自发运动，已经观察到各种不同的模式，包括具有多个伪足突出的变形虫样运动、具有广泛分布的板状伪足的角化细胞样运动、具有两个子细胞向相反方向爬行的细胞分裂以及细胞分裂成多个碎片。突变研究表明，细胞表现出这些模式取决于哪些基因是缺陷的，这表明看似不同的模式是调节细胞运动的共同机制的表现。在本文中，我们提出了一个假设，正反馈机制的工作，通过不均匀分布的调节蛋白的基础上，这种多样性的细胞运动和细胞分裂。在这个假设中，一组我们称之为皮质因子的调节蛋白抑制肌动蛋白聚合。这些抑制因子在细胞的伸展前部被稀释，并在细胞的收缩后部积累，从而建立细胞极性并增强细胞运动性，导致皮质因子在后部进一步积累。细胞运动的随机模拟表明，皮质因素的正反馈机制稳定或不稳定的运动模式，并决定了细胞迁移模式。该模型预测，通过改变肌动蛋白丝网络的形成速率或启动网络形成的阈值来选择模式。
英文摘要：
Eukaryotic cells can move spontaneously without being guided by external cues. For such spontaneous movements, a variety of different modes have been observed, including the amoeboid-like locomotion with protrusion of multiple pseudopods, the keratocyte-like locomotion with a widely spread lamellipodium, cell division with two daughter cells crawling in opposite directions, and fragmentations of a cell to multiple pieces. Mutagenesis studies have revealed that cells exhibit these modes depending on which genes are deficient, suggesting that seemingly different modes are the manifestation of a common mechanism to regulate cell motion. In this paper, we propose a hypothesis that the positive feedback mechanism working through the inhomogeneous distribution of regulatory proteins underlies this variety of cell locomotion and cytofission. In this hypothesis, a set of regulatory proteins, which we call cortical factors, suppress actin polymerization. These suppressing factors are diluted at the extending front and accumulated at the retracting rear of cell, which establishes a cellular polarity and enhances the cell motility, leading to the further accumulation of cortical factors at the rear. Stochastic simulation of cell movement shows that the positive feedback mechanism of cortical factors stabilizes or destabilizes modes of movement and determines the cell migration pattern. The model predicts that the pattern is selected by changing the rate of formation of the actin-filament network or the threshold to initiate the network formation.
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