Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport
Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport
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DOI：
10.1073/pnas.1107841108
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发表时间：
2011-11-22
影响因子：
11.1
通讯作者：
Gross, Steven P.
中科院分区：
文献类型：
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作者：
Kunwar, Ambarish;Tripathy, Suvranta K.;Gross, Steven P.
通过微管马达驱动蛋白和动力蛋白的细胞内运输在维持细胞结构和功能方面起着重要作用。通常，多个驱动蛋白或动力蛋白马达移动相同的货物。它们的集体功能关键取决于负载下单个电机的分离动力学，我们在这里实验测量。这个实验的限制，结合其他实验确定的参数，然后纳入理论随机和平均场模型。建模结果和体外数据的比较显示出良好的协议的随机，但不是平均场，模型。许多货物在体内双向移动，经常逆转路线。由于驱动蛋白和动力蛋白都存在于货物上，一个流行的假说解释了频繁的逆转是，相反极性的马达参与了不受管制的随机拔河比赛。那么，货物的运动就完全可以用这些反向运动竞争的结果来解释了。在这里，我们使用完全校准的随机和平均场模型来测试拔河假设。这两种模型都不符合我们的体内数据，这表明，除了不可避免的拔河比赛之间的相对电机，有一个额外的监管水平不包括在模型中。
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.