A model for intracellular trafficking of adenoviral vectors
A model for intracellular trafficking of adenoviral vectors
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DOI：
10.1529/biophysj.105.059477
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发表时间：
2005-09-01
影响因子：
3.4
通讯作者：
Mitragotri, S
中科院分区：
文献类型：
--
作者：
Dinh, AT;Theofanous, T;Mitragotri, S
在这里，我们开发了一个综合的计算框架，以模拟生物物理过程中涉及的病毒基因传递。该模型结合了反应-扩散-平流方程，描述细胞内的运输与动力学方程，描述转录和翻译的外源DNA。它将分子水平的运输事件与病毒的全细胞分布联系起来。该方法利用了目前对细胞过程的理解和单粒子单细胞成像实验的数据。该模型揭示了两个重要的参数，在人口水平上，即有效速度，V-eff和有效扩散系数，D-eff的病毒运输的特点。V-eff测量病毒的净移动速率，D-eff表示总扩散速率。我们采用该模型研究微管介导的运动对HeLa和A549细胞中2型和5型腺病毒的核靶向和基因表达的影响。微管组织和微管不稳定药物的存在对病毒转运的影响进行了分析和定量。模型预测与文献中的实验数据吻合得很好。该论文为未来理解病毒基因传递的理论和实验工作提供了指导。
Here we develop an integrative computational framework to model biophysical processes involved in viral gene delivery. The model combines reaction-diffusion-advection equations that describe intracellular trafficking with kinetic equations that describe transcription and translation of the exogenous DNA. It relates molecular-level trafficking events to whole-cell distribution of viruses. The approach makes use of the current understanding of cellular processes and data from single-particle single-cell imaging experiments. The model reveals two important parameters that characterize viral transport at the population level, namely, the effective velocity, V-eff, and the effective diffusion coefficient, D-eff. V-eff measures virus's net movement rate and D-eff represents the total dispersion rate. We employ the model to study the influence of microtubule-mediated movements on nuclear targeting and gene expression of adenoviruses of type 2 and type 5 in HeLa and A549 cells. Effects of microtubule organization and the presence of microtubule-destabilizing drugs on viral transport were analyzed and quantified. Model predictions agree well with experimental data available in literature. The paper serves as a guide for future theoretical and experimental efforts to understand viral gene delivery.