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arXiv 1508.02786physics.bio-phq-bio.SC
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三维几何结构对细胞梯度感知和极化的影响

Effects of 3D Geometries on Cellular Gradient Sensing and Polarization

Fabian Spill, Vivi Andasari, Michael Mak, Roger D. Kamm, Muhammad H. Zaman

摘要:

在细胞迁移过程中,细胞变得极化,改变它们的形状,并响应各种内部和外部线索而移动。细胞极化是通过分子如PI3K或小GTP酶的时空组织来定义的,并且由细胞内信号传导网络来确定。它通过肌动蛋白聚合和肌球蛋白收缩产生定向力。许多现有的细胞极化的数学模型是制定在相互作用的分子的反应扩散系统,并经常被定义在一个或两个空间维度。在本文中,我们介绍了一个三维反应扩散模型的相互作用分子在一个单一的细胞,并发现细胞的几何形状有一个重要的作用,影响的能力,细胞的极化,或改变外部信号的方向。我们的研究结果提出了一个几何参数,为什么更多的圆形细胞可以更有效地比沿原始刺激的方向拉长的细胞,从而使圆形细胞转得更快,已经在实验中观察到。另一方面,即使梯度刺激从另一个方向出现,细长的细胞也优先沿其主轴极化。此外,我们的3D模型可以准确地捕获细胞极化的重要调节剂与细胞膜结合和脱离的效果。这种膜和胞质溶胶的空间分离,不可能在1D或2D模型中捕获,导致我们的模型与可比的低维模型有显着差异。

英文摘要:

During cell migration, cells become polarized, change their shape, and move in response to various internal and external cues. Cell polarization is defined through the spatio-temporal organization of molecules such as PI3K or small GTPases, and is determined by intracellular signaling networks. It results in directional forces through actin polymerization and myosin contractions. Many existing mathematical models of cell polarization are formulated in terms of reaction-diffusion systems of interacting molecules, and are often defined in one or two spatial dimensions. In this paper, we introduce a 3D reaction-diffusion model of interacting molecules in a single cell, and find that cell geometry has an important role affecting the capability of a cell to polarize, or change polarization when an external signal changes direction. Our results suggest a geometrical argument why more roundish cells can repolarize more effectively than cells which are elongated along the direction of the original stimulus, and thus enable roundish cells to turn faster, as has been observed in experiments. On the other hand, elongated cells preferentially polarize along their main axis even when a gradient stimulus appears from another direction. Furthermore, our 3D model can accurately capture the effect of binding and unbinding of important regulators of cell polarization to and from the cell membrane. This spatial separation of membrane and cytosol, not possible to capture in 1D or 2D models, leads to marked differences of our model from comparable lower-dimensional models.

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