细胞中病毒和质粒运输的定量分析
Toward a quantitative analysis of virus and plasmid trafficking in cells
摘要:
DNA载体的细胞内运输是基因递送的基本步骤。在这里,我们提出了一个理论方法来研究一般一个单一的病毒或DNA颗粒在细胞质中的运输。细胞运输的实验研究主要是在宏观层面上,但很少有做了到目前为止,在微观层面上。我们在这里提出了一个物理模型来解释细胞组织的某些方面,首先观察到病毒颗粒的轨迹由纯扩散和沿微管主动运输的时期组成。我们定义了一个一般的降解速率来描述质粒或病毒颗粒的细胞质内的各种类型的直接和间接水解活性所施加的限制交付到细胞核。均匀化的过程,其中包括由一个单一的稳态随机描述取代的开关动力学,我们不仅可以研究在胞质溶胶中的移动对象的时空动力学,但也估计的概率和平均时间去从细胞膜到核孔。计算模拟证实,我们的模型可以用来分析和解释病毒的轨迹,并定量估计核交付的成功。
英文摘要:
Intracellular transport of DNA carriers is a fundamental step of gene delivery. We present here a theoretical approach to study generically a single virus or DNA particle trafficking in a cell cytoplasm. Cellular trafficking has been studied experimentally mostly at the macroscopic level, but very little has been done so far at the microscopic level. We present here a physical model to account for certain aspects of cellular organization, starting with the observation that a viral particle trajectory consists of epochs of pure diffusion and epochs of active transport along microtubules. We define a general degradation rate to describe the limitations of the delivery of plasmid or viral particles to the nucleus imposed by various types of direct and indirect hydrolysis activity inside the cytoplasm. Following a homogenization procedure, which consists of replacing the switching dynamics by a single steady state stochastic description, not only can we study the spatio-temporal dynamics of moving objects in the cytosol, but also estimate the probability and the mean time to go from the cell membrane to a nuclear pore. Computational simulations confirm that our model can be used to analyze and interpret viral trajectories and estimate quantitatively the success of nuclear delivery.
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