Sliding of motor tails on cargo surface due to drift and diffusion affects their team arrangement and collective transport

Abstract

Abstract 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. Various in-vitro and 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.