Hafner Anne E, Rieger Heiko
Department of Theoretical Physics, Saarland University, D-66123 Saarbrücken, Germany.
Phys Biol. 2016 Nov 15;13(6):066003. doi: 10.1088/1478-3975/13/6/066003.
Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell's specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.
细胞内运输对于细胞的正常功能和存活至关重要。货物（蛋白质、囊泡、细胞器等）通过沿细胞骨架细丝的分子马达辅助运输从其产生位置转移到目标位置。运输效率受到细胞骨架空间组织的强烈影响，细胞骨架构成了一个不均匀的复杂网络。在具有中心体的细胞中，微管从中央微管组织中心径向向细胞周边生长，而肌动蛋白丝在细胞膜下方形成密集的网络，即肌动蛋白皮层，其取向范围广泛。由于拥挤细胞质中的收缩交叉节点或脱离和重新附着过程的循环，沿细丝出现的弹道运动经常被打断。为了研究细胞骨架特定空间组织建立的搜索策略的效率，我们制定了一个具有间歇性停滞状态的随机速度模型。通过广泛的计算机模拟，我们分析了窄逃逸问题的平均首次通过时间对细胞骨架结构特征、马达特性以及在每种状态下花费的时间分数的依赖性。我们发现，具有窄肌动蛋白皮层宽度的不均匀结构构成了一种有效的细胞内搜索策略。
