Department of Mathematics, University of Florida, Gainesville, FL, USA.
Department of Mathematics, Tulane University, New Orleans, LA, USA.
Bull Math Biol. 2018 Aug;80(8):2088-2123. doi: 10.1007/s11538-018-0448-9. Epub 2018 Jun 4.
The bidirectional movement of intracellular cargo is usually described as a tug-of-war among opposite-directed families of molecular motors. While tug-of-war models have enjoyed some success, recent evidence suggests underlying motor interactions are more complex than previously understood. For example, these tug-of-war models fail to predict the counterintuitive phenomenon that inhibiting one family of motors can decrease the functionality of opposite-directed transport. In this paper, we use a stochastic differential equations modeling framework to explore one proposed physical mechanism, called microtubule tethering, that could play a role in this "co-dependence" among antagonistic motors. This hypothesis includes the possibility of a trade-off: weakly bound trailing molecular motors can serve as tethers for cargoes and processing motors, thereby enhancing motor-cargo run lengths along microtubules; however, this introduces a cost of processing at a lower mean velocity. By computing the small- and large-time mean-squared displacement of our theoretical model and comparing our results to experimental observations of dynein and its "helper protein" dynactin, we find some supporting evidence for microtubule tethering interactions. We extrapolate these findings to predict how dynein-dynactin might interact with the opposite-directed kinesin motors and introduce a criterion for when the trade-off is beneficial in simple systems.
细胞内货物的双向运动通常被描述为相反方向的分子马达家族之间的拔河比赛。虽然拔河模型取得了一些成功，但最近的证据表明，潜在的马达相互作用比以前理解的要复杂。例如，这些拔河模型无法预测反直觉的现象，即抑制一种马达家族会降低相反方向运输的功能。在本文中，我们使用随机微分方程建模框架来探索一种被称为微管系绳的物理机制，该机制可能在拮抗马达之间的这种“相互依赖”中发挥作用。该假设包括一种权衡的可能性：弱结合的尾随分子马达可以作为货物和加工马达的系绳，从而增强货物沿着微管的马达运行长度；然而，这会以较低的平均速度为代价引入处理成本。通过计算我们理论模型的小时间和大时间均方位移，并将我们的结果与动力蛋白及其“辅助蛋白”dynactin 的实验观察进行比较，我们发现了一些支持微管系绳相互作用的证据。我们推断这些发现来预测动力蛋白 dynactin 如何与相反方向的驱动蛋白马达相互作用，并引入一个简单系统中何时权衡是有益的标准。
