Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India.
Phys Biol. 2022 Nov 7;20(1). doi: 10.1088/1478-3975/ac99b2.
Kinesin is a microtubule-associated motor protein which works in teams to carry the cellular cargo transport. Lipid rafts on membranous cargos reorganize, causing the motors present in these areas to physically cluster. Unregulated clustering of motors leads to diseases such as Leishmaniasis, Newmann-Pick disease, etc. Variousand computational studies have reported improved cargo velocity and travel distance of a fluid cargo as compared to a rigid cargo. However, only cargo velocity increases with increase in membrane fluidity of a fluid cargo. Thermal and motor forces acting tangentially on a cargo generate random torque and motor torque respectively, leading to cargo rotation and motor tail sliding on cargo surface. However, it is unknown which of these forces/torques play a crucial role in improving the transport properties. Here, we use computational models that incorporate random torque, motor torque, and combination of both random and motor torques to understand how they influence the clustering of Kinesin motors on cargo surface due to drift and diffusion of their tails. These studies were performed at varying tail diffusivity to understand their effect on clustering of tails in dispersed and clustered arrangement. We find that in dispersed arrangement, random torque does not cause clustering, whereas motor torque is crucial for clustering of tails on cargo surface, and tails sliding due to both random and motor torques have fastest cargo transport and maximum cooperativity. In clustered arrangement, tails slide to form a broad and steady cluster whose size increases with tail diffusivity resulting in decreased cargo runlength, velocity and cooperativity. These findings suggest that increased tail diffusivity negatively impacts the cluster and cargo transport of tails in the clustered arrangement, whereas it aids physical clustering of tails and cargo transport in dispersed arrangement.
驱动蛋白是一种微管相关的运动蛋白，它协同工作以进行细胞货物运输。膜状货物上的脂质筏重新组织，导致存在于这些区域的马达物理聚集。马达不受控制的聚集会导致疾病，如利什曼病、尼曼-匹克病等。各种计算研究报告称，与刚性货物相比，流体货物的货物速度和行驶距离得到了提高。然而，只有随着流体货物膜流动性的增加，货物速度才会增加。作用于货物的热和马达力沿切线方向产生随机扭矩和马达扭矩，分别导致货物旋转和马达尾部在货物表面滑动。然而，尚不清楚这些力/扭矩中的哪一个在提高运输性能方面起着关键作用。在这里，我们使用包含随机扭矩、马达扭矩以及随机扭矩和马达扭矩组合的计算模型，以了解它们如何由于尾部的漂移和扩散而影响 Kinesin 马达在货物表面的聚集。这些研究是在不同的尾部扩散系数下进行的，以了解它们对尾部在分散和聚集排列中的聚集的影响。我们发现，在分散排列中，随机扭矩不会引起聚集，而马达扭矩对于货物表面上尾部的聚集至关重要，并且由于随机和马达扭矩导致的尾部滑动具有最快的货物运输和最大的协同性。在聚集排列中，尾部滑动形成一个宽阔而稳定的簇，其大小随尾部扩散系数的增加而增加，导致货物运行长度、速度和协同性降低。这些发现表明，增加的尾部扩散性对聚集排列中尾部的簇和货物运输产生负面影响，而在分散排列中，它有助于尾部和货物的物理聚集。
