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Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport

机译:机械随机拔河模型无法解释双向脂滴运输

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摘要

Intracellular transport via the microtubule motors kinesin and dynein plays an important role in maintaining cell structure and function. Often, multiple kinesin or dynein motors move the same cargo. Their collective function depends critically on the single motors’ detachment kinetics under load, which we experimentally measure here. This experimental constraint—combined with other experimentally determined parameters—is then incorporated into theoretical stochastic and mean-field models. Comparison of modeling results and in vitro data shows good agreement for the stochastic, but not mean-field, model. Many cargos in vivo move bidirectionally, frequently reversing course. Because both kinesin and dynein are present on the cargos, one popular hypothesis explaining the frequent reversals is that the opposite-polarity motors engage in unregulated stochastic tugs-of-war. Then, the cargos’ motion can be explained entirely by the outcome of these opposite-motor competitions. Here, we use fully calibrated stochastic and mean-field models to test the tug-of-war hypothesis. Neither model agrees well with our in vivo data, suggesting that, in addition to inevitable tugs-of-war between opposite motors, there is an additional level of regulation not included in the models.
机译:通过微管马达的细胞内运输驱动蛋白和动力蛋白在维持细胞结构和功能中起重要作用。通常,多个驱动蛋白或动力蛋白马达可移动同一货物。它们的集体功能主要取决于单个电动机在负载下的分离动力学,我们在这里通过实验对其进行测量。然后将此实验约束条件与其他实验确定的参数结合起来,并纳入理论随机模型和均值模型。建模结果与体外数据的比较表明,随机模型与均值模型具有很好的一致性。体内的许多货物都是双向移动的,经常会反向移动。由于货物中同时存在驱动蛋白和动力蛋白,因此一种常见的解释频繁反转的假说是,相反极性的电动机会参与不受管制的随机拔河。然后,这些反向运动竞赛的结果可以完全解释这些货物的运动。在这里,我们使用完全校准的随机模型和均值模型来测试拔河假设。这两个模型都与我们的体内数据不一致,这表明,除了相对马达之间不可避免的拔河比赛外,模型中还没有附加的调节水平。

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