Department of Physics, University of California Merced, Merced California, USA.
Department of Physics, University of Northern Iowa, Cedar Falls Iowa, USA.
Phys Rev E. 2019 Jun;99(6-1):062404. doi: 10.1103/PhysRevE.99.062404.
Intracellular transport in eukaryotic cells consists of phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton. The interplay between superdiffusive transport along cytoskeletal filaments and the anomalous nature of subdiffusion in the bulk can lead to novel effects in transport behavior at the cellular scale. Here we develop a computational model of the process with cargo being ballistically transported along explicitly modeled cytoskeletal filament networks and passively transported in the cytoplasm by a subdiffusive continuous-time random walk (CTRW). We show that, over a physiologically relevant range of filament lengths and numbers, the network introduces a filament-length sensitive superdiffusive phase at early times which crosses over to a phase where the CTRW is dominant and produces subdiffusion at late times. We apply our approach to the problem of insulin secretion from cells and show that the superdiffusive phase introduced by the filament network manifests as a peak in the secretion at early times followed by an extended sustained release phase that is dominated by the CTRW process at late times. Our results are consistent with in vivo observations of insulin transport in healthy cells and shed light on the potential for the cell to tune functionally important transport phases by altering its cytoskeletal network.
真核细胞内的物质运输由被动的扩散运输和主动的、沿细胞骨架丝状结构的马达驱动运输两个阶段组成。沿着细胞骨架丝状结构的超扩散运输与整体亚扩散的异常性质之间的相互作用，可能会导致细胞尺度上的物质运输行为产生新的效应。在这里，我们建立了一个包含货物沿明确建模的细胞骨架丝状网络弹道运输和在细胞质中通过亚扩散连续时间随机行走（CTRW）被动运输的计算模型。我们表明，在生理相关的丝状长度和数量范围内，网络在早期引入了一个丝状长度敏感的超扩散相，然后过渡到一个 CTRW 占主导地位并在后期产生亚扩散的相。我们将我们的方法应用于胰岛素从细胞分泌的问题，并表明丝状网络引入的超扩散相表现为早期分泌的峰值，然后是一个扩展的持续释放相，在后期由 CTRW 过程主导。我们的结果与健康细胞中胰岛素运输的体内观察结果一致，并阐明了细胞通过改变其细胞骨架网络来调节功能重要的运输相的潜力。
