Ando David, Korabel Nickolay, Huang Kerwyn Casey, Gopinathan Ajay
Department of Physics, University of California, Merced, California.
Department of Physics, University of California, Merced, California; School of Mathematics, University of Manchester, Manchester, United Kingdom.
Biophys J. 2015 Oct 20;109(8):1574-82. doi: 10.1016/j.bpj.2015.08.034.
Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design.
在大多数真核细胞中，细胞内运输对于维持正常的细胞功能至关重要，主动运输的扰动会导致多种疾病。通过被动扩散和分子马达的主动运输相结合，关键货物被高效地运送到特定位置，分子马达沿着细胞骨架丝网络进行弹道式移动。虽然已知基于马达的运输对于在合理的时间尺度内克服细胞质拥挤和有限的扩散范围是必要的，但调节运输效率和稳健性的细胞骨架网络的拓扑特征尚未明确。使用连续扩散模型，我们观察到当网络位于细胞核附近时，细胞运输所需的时间最短。在明确纳入网络空间结构的模拟中，总细丝质量是网络运输时间 的主要驱动因素。然而，将货物重定向回细胞核的细丝陷阱会导致网络运输出现很大变化。在减少平均运输时间方面，细丝极性比细丝方向更重要，并且在马达开启和关闭速率适中的网络中运输特性得到了优化。我们 的结果为细胞进化出细胞骨架结构的细胞内运输功能限制提供了重要见解，并通过合理的运输网络设计在增强仿生系统中的反应方面具有潜在应用。
