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使用反应扩散方程对 T 淋巴细胞内时空钙分布进行建模与仿真。

Modeling and simulation of spatial-temporal calcium distribution in T lymphocyte cell by using a reaction-diffusion equation.

机构信息

School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P. R. China.

出版信息

J Bioinform Comput Biol. 2020 Apr;18(2):2050013. doi: 10.1142/S0219720020500134. Epub 2020 May 6.

Abstract

T lymphocytes are white blood cells that play a central role in cell-mediated immunity. Ca has its major signaling function when it is elevated in the cytosolic compartment. The free cytosolic Ca dynamics plays a very important role in the activation, and fate decision process in the T lymphocytes. Here, we develop a quantitative spatio-temporal Ca dynamic model which includes, the Ca releasing channels ER leak and voltage-gated Ca channel, buffering and re-uptaking mechanism in the T lymphocytes. In this model, the cell is represented as a circular-shaped geometrical domain. This representation introduces modeling flexibility needed for detailed representation of the properties of Ca dynamics in the cell including important parameters. The proposed mathematical model is solved using a finite difference method and the finite element method. Appropriate initial and boundary conditions are incorporated in the model based on biophysical conditions of the problem. Computer simulations in MATLAB R2010a are employed to investigate mathematical models of reaction-diffusion equation. The estimation is based on reaction-diffusion equation associated with biophysical and biochemical reactions taking place in the cell. From our results, it is observed that, the coordinated combination of the incorporated parameters plays a significant role in Ca regulation in T lymphocytes. ER leak and voltage-gated Ca channel provides the necessary Ca to the cell when required for its proper functioning, while on the other side buffers and Na/Ca exchanger makes balance in the Ca concentration, so as to prevent the cell from death as higher concentration for longer time is harmful for the cell and can cause cell death. These results have been used to study the relationship of Ca concentration with parameters like VGCC, Na/Ca exchanger, ER leak and buffers. The significance of the study reveals that there is a significant variation in Ca profiles due to the effect of VGCC, Na/Ca exchanger, ER leak, and buffers. The results give us better insights of coordinated effect of VGCC, Na/Ca exchanger, ER leak, and buffers on Ca distribution in T lymphocytes. T lymphocytes are the primary host cells to receive the viral infections which transmits the signal then to other cell types. The proper quantity of Ca concentration makes T lymphocytes more active and healthier to fight the infection properly and can protect the immune system from various fatal viral infections. Thus, the application of the study lies in the field of immunology to protect a susceptible from various viral infectious diseases like HIV, HBV, HINI, etc. by strengthening the immune system. The outcomes of the study reveal that the applied finite element method is computationally very strong and effective to analyze differential equations that arise in Ca dynamics.

摘要

T 淋巴细胞是白细胞,在细胞介导的免疫中起着核心作用。当细胞溶质中的 Ca 升高时,它具有主要的信号功能。游离细胞溶质 Ca 动力学在 T 淋巴细胞的激活和命运决策过程中起着非常重要的作用。在这里,我们开发了一个定量的时空 Ca 动态模型,该模型包括 T 淋巴细胞中的 Ca 释放通道 ER 渗漏和电压门控 Ca 通道、缓冲和再摄取机制。在这个模型中,细胞被表示为一个圆形的几何区域。这种表示法为详细表示细胞内 Ca 动力学的特性引入了建模的灵活性,包括重要的参数。所提出的数学模型使用有限差分法和有限元法求解。根据问题的生物物理条件,在模型中加入适当的初始和边界条件。在 MATLAB R2010a 中进行计算机模拟,以研究反应扩散方程的数学模型。该估计基于发生在细胞中的反应-扩散方程以及生物物理和生化反应。从我们的结果可以看出,所包含参数的协调组合在 T 淋巴细胞的 Ca 调节中起着重要作用。当 T 淋巴细胞正常运作需要 Ca 时,ER 渗漏和电压门控 Ca 通道会为细胞提供必要的 Ca,而另一方面,缓冲液和 Na/Ca 交换器会使 Ca 浓度保持平衡,以防止细胞因长时间高浓度而死亡,因为更高的浓度对细胞有害,并可能导致细胞死亡。这些结果已被用于研究 Ca 浓度与 VGCC、Na/Ca 交换器、ER 渗漏和缓冲液等参数之间的关系。研究的意义在于,由于 VGCC、Na/Ca 交换器、ER 渗漏和缓冲液的影响,Ca 谱会发生显著变化。结果使我们对 VGCC、Na/Ca 交换器、ER 渗漏和缓冲液对 T 淋巴细胞内 Ca 分布的协调作用有了更好的了解。T 淋巴细胞是接收病毒感染的主要宿主细胞,它会将信号传递给其他细胞类型。适当的 Ca 浓度使 T 淋巴细胞更活跃、更健康,从而能够更好地对抗感染,并保护免疫系统免受各种致命的病毒性感染。因此,该研究的应用在于免疫学领域,通过增强免疫系统来保护易感人群免受各种病毒性传染病的侵害,如 HIV、HBV、HINI 等。研究结果表明,所应用的有限元方法在分析 Ca 动力学中出现的微分方程方面具有很强的计算能力和有效性。

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