Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models
Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models
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DOI：
10.1088/1478-3975/12/6/066014
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发表时间：
2015-12-01
期刊：
影响因子：
2
通讯作者：
Klipp, Edda
中科院分区：
文献类型：
--
作者：
Giese, Wolfgang;Eigel, Martin;Klipp, Edda
在硅片实验承担进一步了解生物运输过程的潜力，允许任何空间属性的系统修改，并提供即时的模拟结果。细胞极化和膜蛋白的空间重组是细胞分裂、趋化性和形态发生的基础。我们选择酵母酿酒酵母作为示例性的模型系统，其需要小Rho GTP酶如Cdc 42和Rho在活性膜结合形式和非活性胞质形式之间穿梭。我们使用偏微分方程来描述蛋白质的膜-胞质溶胶穿梭。本文将一类一维反应扩散方程组一致推广到高维空间。膜被建模为薄层以允许侧向扩散，并且细胞溶质被建模为封闭体积。两个众所周知的极化机制被认为是。一个显示了经典的图灵不稳定性模式，另一个表现出波钉扎动力学。对于这两种模型，我们研究了细胞形状和扩散障碍，如隔蛋白结构或芽痕如何影响信号分子簇的形成和随后的极化。一个广泛的一组在电脑实验与不同的建模假设说明了依赖于局部膜曲率，细胞大小和不均匀性的膜和细胞质中的细胞极化模型。特别是，我们的计算机模拟的结果表明，对于这两种机制，膜上的局部扩散障碍促进Rho GTdR聚集，而在胞质溶胶和细胞突起的扩散障碍限制自发分子聚集的活性Rho GTdR本地。
In silico experiments bear the potential for further understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results. Cell polarization and spatial reorganization of membrane proteins are fundamental for cell division, chemotaxis and morphogenesis. We chose the yeast Saccharomyces cerevisiae as an exemplary model system which entails the shuttling of small Rho GTPases such as Cdc42 and Rho, between an active membrane-bound form and an inactive cytosolic form. We used partial differential equations to describe the membrane-cytosol shuttling of proteins. In this study, a consistent extension of a class of 1D reaction-diffusion systems into higher space dimensions is suggested. The membrane is modeled as a thin layer to allow for lateral diffusion and the cytosol is modeled as an enclosed volume. Two well-known polarization mechanisms were considered. One shows the classical Turing-instability patterns, the other exhibits wave-pinning dynamics. For both models, we investigated how cell shape and diffusion barriers like septin structures or bud scars influence the formation of signaling molecule clusters and subsequent polarization. An extensive set of in silico experiments with different modeling hypotheses illustrated the dependence of cell polarization models on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. In particular, the results of our computer simulations suggested that for both mechanisms, local diffusion barriers on the membrane facilitate Rho GTPase aggregation, while diffusion barriers in the cytosol and cell protrusions limit spontaneous molecule aggregations of active Rho GTPase locally.