Lagache Thibault, Dauty Emmanuel, Holcman David
Département de Mathématiques et de Biologie, Ecole Normale Supérieure, 46 rue d'Ulm 75005 Paris, France.
Phys Rev E Stat Nonlin Soft Matter Phys. 2009 Jan;79(1 Pt 1):011921. doi: 10.1103/PhysRevE.79.011921. Epub 2009 Jan 28.
Intracellular transport of DNA carriers is a fundamental step of gene delivery. By combining both theoretical and numerical approaches we study here single and several viruses and DNA particles trafficking in the cell cytoplasm to a small nuclear pore. We present a physical model to account for certain aspects of cellular organization, starting with the observation that a viral 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 a nuclear pore imposed by various types of direct and indirect hydrolysis activity inside the cytoplasm. By replacing the switching dynamics by a single steady state stochastic description, we obtain estimates for the probability and the mean time for the first one of many particles to go from the cell membrane to a small 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.
DNA载体的细胞内运输是基因递送的一个基本步骤。通过结合理论和数值方法，我们在此研究单个及多个病毒和DNA颗粒在细胞质中向小核孔的运输。我们提出一个物理模型来解释细胞组织的某些方面，首先观察到病毒轨迹由纯扩散时期和沿微管的主动运输时期组成。我们定义了一个一般降解率来描述细胞质内各种直接和间接水解活性对质粒或病毒颗粒递送至核孔的限制。通过用单一稳态随机描述取代切换动力学，我们获得了许多颗粒中第一个从细胞膜到达小核孔的概率和平均时间的估计值。计算模拟证实，我们的模型可用于分析和解释病毒轨迹，并定量估计核递送的成功率。
