Jensen Melanie A, Feng Qingzhou, Hancock William O, McKinley Scott A
Department of Mathematics, Tulane University, New Orleans, LA 70118, USA.
Schlumberger, 1 Hampshire St Ste 1, Cambridge, MA, 02319 USA.
Math Biosci Eng. 2021 Oct 18;18(6):8962-8996. doi: 10.3934/mbe.2021442.
Intracellular transport by microtubule-based molecular motors is marked by qualitatively different behaviors. It is a long-standing and still-open challenge to accurately quantify the various individual-cargo behaviors and how they are affected by the presence or absence of particular motor families. In this work we introduce a protocol for analyzing change points in cargo trajectories that can be faithfully projected along the length of a (mostly) straight microtubule. Our protocol consists of automated identification of velocity change points, estimation of velocities during the behavior segments, and extrapolation to motor-specific velocity distributions. Using simulated data we show that our method compares favorably with existing methods. We then apply the technique to data sets in which quantum dots are transported by Kinesin-1, by Dynein-Dynactin-BicD2 (DDB), and by Kinesin-1/DDB pairs. In the end, we identify pausing behavior that is consistent with some tug-of-war model predictions, but also demonstrate that the simultaneous presence of antagonistic motors can lead to long processive runs that could contribute favorably to population-wide transport.
基于微管的分子马达进行的细胞内运输具有质的不同行为。准确量化各种单个货物的行为以及它们如何受到特定马达家族存在与否的影响,这是一个长期存在且仍未解决的挑战。在这项工作中,我们介绍了一种分析货物轨迹变化点的方案,这些轨迹可以沿着(大部分)笔直的微管长度进行准确投影。我们的方案包括自动识别速度变化点、估计行为段期间的速度以及外推到特定马达的速度分布。使用模拟数据,我们表明我们的方法优于现有方法。然后,我们将该技术应用于量子点由驱动蛋白-1、动力蛋白-动力蛋白激活蛋白-BicD2(DDB)以及驱动蛋白-1/DDB对运输的数据集。最后,我们识别出与一些拔河模型预测一致的暂停行为,但同时也证明了拮抗马达的同时存在可以导致长距离的连续运行,这可能对群体范围内的运输产生有利影响。