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通过微管交叉处对集体运动蛋白运输进行随机建模。

Stochastic modelling of collective motor protein transport through a crossing of microtubules.

作者信息

Raguin Adélaïde, Kern Norbert, Parmeggiani Andrea

机构信息

L2C, University of Montpellier, CNRS, Montpellier, France; LPHI, University of Montpellier, CNRS, INSERM, Montpellier, France; Institute of Quantitative and Theoretical Biology, Department of Biology, Heinrich-Heine University, Düsseldorf 40225, Germany.

L2C, University of Montpellier, CNRS, Montpellier, France.

出版信息

J Theor Biol. 2020 Nov 21;505:110370. doi: 10.1016/j.jtbi.2020.110370. Epub 2020 Jun 17.

Abstract

The cytoskeleton in eukaryotic cells plays several crucial roles. In terms of intracellular transport, motor proteins use the cytoskeletal filaments as a backbone along which they can actively transport biological cargos such as vesicles carrying biochemical reactants. Crossings between such filaments constitute a key element, as they may serve to alter the destination of such payload. Although motor proteins are known to display a rich behaviour at such crossings, the latter have so far only been modelled as simple branching points. Here we explore a model for a crossing between two microtubules which retains the individual tracks consisting of protofilaments, and we construct a schematic representation of the transport paths. We study collective transport exemplified by the Totally Asymmetric Simple Exclusion Process (TASEP), and provide a full analysis of the transport features and the associated phase diagram, by a generic mean-field approach which we confirm through particle-based stochastic simulations. In particular we show that transport through such a compound crossing cannot be approximated from a coarse-grained structure with a simple branching point. Instead, it gives rise to entirely new and counterintuitive features: the fundamental current-density relation for traffic flow is no longer a single-valued function, and it furthermore differs according to whether it is observed upstream or downstream from the crossing. We argue that these novel features may be directly relevant for interpreting experimental measurements.

摘要

真核细胞中的细胞骨架发挥着几个关键作用。在细胞内运输方面,驱动蛋白利用细胞骨架丝作为主干,沿着它可以主动运输生物货物,如携带生化反应物的囊泡。这些丝之间的交叉点是一个关键要素,因为它们可能用于改变此类货物的目的地。尽管已知驱动蛋白在这些交叉点表现出丰富的行为,但到目前为止,后者仅被建模为简单的分支点。在这里,我们探索了一种两个微管之间交叉的模型,该模型保留了由原纤维组成的单独轨道,并构建了运输路径的示意图。我们研究了以完全非对称简单排斥过程(TASEP)为例的集体运输,并通过一种通用的平均场方法对运输特征和相关相图进行了全面分析,我们通过基于粒子的随机模拟对该方法进行了验证。特别是我们表明,通过这种复合交叉点的运输不能从具有简单分支点的粗粒度结构进行近似。相反,它产生了全新的、违反直觉的特征:交通流的基本电流 - 密度关系不再是单值函数,而且根据在交叉点上游还是下游观察,它也有所不同。我们认为这些新特征可能与解释实验测量直接相关。

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