会聚微管形态上的可调细胞内运输
Tunable intracellular transport on converging microtubule morphologies
摘要:
一种常见的细胞骨架形态包括多个会聚的微管,其负端由细胞内部的微管组织中心(MTOC)收集和稳定。这种排列使得结合到微管的货物的弹道运输成为可能,动力蛋白介导的朝向MTOC的运输和驱动蛋白介导的远离MTOC的运输两者,穿插有未结合的货物-马达复合物的扩散。MTOC的空间和时间定位允许朝向和远离细胞内特定细胞器和位置的双向运输,以及动力蛋白运输货物的隔离和随后的分散。在海洋技术选择委员会附近,这种运输的动力学、效率和可调性的一般原则尚未完全了解。为了解决这个问题,我们开发了一个一维模型,其中包括对吸引子(如MTOC)的平流运输,以及允许颗粒到达吸收边界(如细胞膜)的扩散运输。我们计算了货物到达边界的平均首次通过时间(MFPT),以衡量隔离(大MFPT)和扩散扩散(低MFPT)的有效性。MFPT经历了幅度的急剧增长,在接近体内值的货物附着/脱离速率的窗口上从低MFPT状态(分散到隔离)过渡到高MFPT状态。我们发现,增加附着或分离率,而固定的其他,可以导致最佳的分散时,吸引子放置不对称。最后,我们描述了一个罕见的事件政权,逃逸的位置是指数敏感的吸引子定位。我们的研究结果表明,结构,如MTOC允许敏感控制的空间和时间的特点,运输和相应的功能在生理条件下。
英文摘要:
A common type of cytoskeletal morphology involves multiple converging microbutubules with their minus ends collected and stabilized by a microtubule organizing center (MTOC) in the interior of the cell. This arrangement enables the ballistic transport of cargo bound to microtubules, both dynein mediated transport towards the MTOC and kinesin mediated transport away from it, interspersed with diffusion for unbound cargo-motor complexes. Spatial and temporal positioning of the MTOC allows for bidirectional transport towards and away from specific organelles and locations within the cell and also the sequestering and subsequent dispersal of dynein transported cargo. The general principles governing dynamics, efficiency and tunability of such transport in the MTOC vicinity is not fully understood. To address this, we develop a one-dimensional model that includes advective transport towards an attractor (such as the MTOC), and diffusive transport that allows particles to reach absorbing boundaries (such as cellular membranes). We calculated the mean first passage time (MFPT) for cargo to reach the boundaries as a measure of the effectiveness of sequestering (large MFPT) and diffusive dispersal (low MFPT). The MFPT experiences a dramatic growth in magnitude, transitioning from a low to high MFPT regime (dispersal to sequestering) over a window of cargo attachment/detachment rates that is close to in vivo values. We find that increasing either the attachment or detachment rate, while fixing the other, can result in optimal dispersal when the attractor is placed asymmetrically. Finally, we describe a rare event regime, where the escape location is exponentially sensitive to the attractor positioning. Our results suggest that structures such as the MTOC allow for the sensitive control of the spatial and temporal features of transport and corresponding function under physiological conditions.
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