Dynamics of Intracellular Nano-Transport by Kinesins

[摘要] Transport in neurons is realized by motor proteins (kinesins) which walk along intracellular tracks. Healthy mechanical transport is necessary for neurons to maintain their normal functions. Degradation of this transport is believed to result in neurodegenerative diseases such as Alzheimer;;s disease. One possible cause for the degradation is the presence of molecules such as tau proteins attached to the surfaces of the intracellular tracks. It is observed that tau proteins interrupt the motion of kinesin both in vitro and in vivo experiments. In this dissertation, a new physics-based mathematical model is developed to study the effects of obstacles on the intracellular transport. This newly developed model considers various motions of kinesins in cells; walking on the track, unbinding from the track, thermally fluctuating motion (when they are not bound on the track), and binding again to the track.Kinesins unbind from the track when they encounter clusters of tau proteins. However, kinesins can bind to other locations of the track in a very short time, especially the kinesins which are attached to small cargoes. A quantitative study reveals that the decrease in the average velocity is not considerable until the tracks are crowded with large numbers of obstacles. Despite the small change in the average velocity, kinesin motion is modified by the obstacles. The model predicted that the transport of the cargo is delayed in front (upstream) of clusters of tau proteins, and the transport is likely to be fast behind (downstream) the clusters. Also, the results show that the regional delays can be detected with a low precision which is much longer than the step size of kinesins. The predicted behavior of kinesins near obstacles and the proposed method to characterize that behavior can open the door to an easier means to estimate the state of health of the transport system in neuron.

[发布机构] University of Michigan

[效力级别] Intracellular transport

[关键词] Kinesin;Intracellular transport;Tau protein;Alzheimer"s disease;Biomedical Engineering;Mechanical Engineering;Engineering;Science;Mechanical Engineering