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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Spatial modeling of dimerization reaction dynamics in the plasma membrane: Monte Carlo vs. continuum differential equations
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Spatial modeling of dimerization reaction dynamics in the plasma membrane: Monte Carlo vs. continuum differential equations

机译：质膜中二聚化反应动力学的空间模型：蒙特卡洛与连续介质微分方程

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Bimolecular reactions in the plasma membrane, such as receptor dimerization, are a key signaling step for many signaling systems. For receptors to dimerize, they must first diffuse until a collision happens, upon which a dimerization reaction may occur. Therefore, study of the dynamics of cell signaling on the membrane may require the use of a spatial modeling framework. Despite the availability of spatial simulation methods, e.g., stochastic spatial Monte Carlo (MC) simulation and partial differential equation (PDE) based approaches, many biological models invoke well-mixed assumptions without completely evaluating the importance of spatial organization. Whether one is to utilize a spatial or non-spatial simulation framework is therefore an important decision. In order to evaluate the importance of spatial effects a priori, i.e., without performing simulations, we have assessed the applicability of a dimensionless number, known as second Damkohler number (Da), defined here as the ratio of time scales of collision and reaction, for 2-dimensional bimolecular reactions. Our study shows that dimerization reactions in the plasma membrane with Da similar to > 0.1 (tested in the receptor density range of 10(2)-10(5)/mu m(2)) require spatial modeling. We also evaluated the effective reaction rate constants of MC and simple deterministic PDEs. Our simulations show that the effective reaction rate constant decreases with time due to time dependent changes in the spatial distribution of receptors. As a result, the effective reaction rate constant of simple PDEs can differ from that of MC by up to two orders of magnitude. Furthermore, we show that the fluctuations in the number of copies of signaling proteins (noise) may also depend on the diffusion properties of the system. Finally, we used the spatial MC model to explore the effect of plasma membrane heterogeneities, such as receptor localization and reduced diffusivity, on the dimerization rate. Interestingly, our simulations show that localization of epidermal growth factor receptor (EGFR) can cause the diffusion limited dimerization rate to be up to two orders of magnitude higher at higher average receptor densities reported for cancer cells, as compared to a normal cell. (c) 2006 Elsevier B.V. All rights reserved.
机译：质膜中的双分子反应，例如受体二聚化，是许多信号系统的关键信号步骤。为了使受体二聚化，它们必须首先扩散直至发生碰撞，此后可能发生二聚化反应。因此，对膜上细胞信号传导动力学的研究可能需要使用空间建模框架。尽管有可用的空间模拟方法，例如基于随机空间蒙特卡洛（MC）模拟和基于偏微分方程（PDE）的方法，但许多生物学模型在没有完全评估空间组织重要性的情况下调用了充分混合的假设。因此，是利用空间仿真框架还是非空间仿真框架是一个重要的决定。为了先验地评估空间效应的重要性，即在不执行模拟的情况下，我们评估了无量纲数（称为第二达姆霍勒数（Da））的适用性，此处将其定义为碰撞和反应的时间尺度之比，用于二维双分子反应。我们的研究表明，质膜中Da大于> 0.1的二聚反应（在10（2）-10（5）/μm（2）的受体密度范围内测试）需要空间建模。我们还评估了MC和简单确定性PDE的有效反应速率常数。我们的模拟表明，由于受体空间分布的时间依赖性变化，有效反应速率常数随时间而降低。结果，简单PDE的有效反应速率常数可能与MC的有效反应速率常数相差最多两个数量级。此外，我们表明信号蛋白（噪声）的拷贝数波动也可能取决于系统的扩散特性。最后，我们使用空间MC模型探索质膜异质性（如受体定位和降低的扩散率）对二聚化率的影响。有趣的是，我们的模拟显示表皮生长因子受体（EGFR）的定位与正常细胞相比，在癌细胞报道的较高平均受体密度下，可导致扩散受限的二聚化率高出两个数量级。 （c）2006 Elsevier B.V.保留所有权利。

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