Dynamic model for kinesin-mediated long-range transport and its local traffic jam caused by tau proteins.
Dynamic model for kinesin-mediated long-range transport and its local traffic jam caused by tau proteins.
复制标题
驱动蛋白介导的长距离运输及其由 tau 蛋白引起的局部交通堵塞的动态模型。
DOI：
10.1103/physreve.95.012405
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
B. Epureanu
中科院分区：
文献类型：
--
作者：
Woochul Nam;B. Epureanu
在神经元中，一些细胞内的货物是由行走在微管上的运动蛋白（运动蛋白）运输的。然而，运动蛋白可能在mt到达目的地之前就与它们分离。未结合的运动蛋白在神经元中随机扩散，直到它们与mt结合。然后，它们沿着mt再次行走，继续它们的任务。运动学重复这个运动循环，直到它们把货物运送到目的地。然而，以往大多数模型主要关注运动蛋白在mt上行走时的运动，因此，需要一个新的模型来涵盖各种类型的运动蛋白。我们建立了一个综合模型，并利用该模型研究了神经元的远端轴突转运。为提高模型的可靠性，基于动力学的多物理场（即化学动力学、扩散动力学、流体动力学、非线性动力学和随机特性）构建了模型。此外，通过比较模型预测和几个实验观察，仔细地获得了运动学的参数值。当mt上的大量结合位点被过量的tau蛋白阻断时，轴突运输就会被降解。通过考虑行走驱动蛋白和tau分子对MTs的干扰，研究了tau蛋白对轴突运输的影响。从模型中得到的一个有意义的预测是，速度不是估计运输降解的有效指标，因为当tau蛋白浓度不高时，速度的降低并不明显。然而，我们的模型表明，即使速度变化不显著，mt上tau分子附近的输运也会发生局部变化。因此，提出了一种有效检测这种局部变化的统计方法。该方法的优点是该方法获得的值对tau蛋白的浓度高度敏感。该方法的另一个优点是，考虑到运动的时间尺度和长度尺度，可以以相对较低的精度和较低的时间分辨率获得这个高度敏感的值。该方法可用于估计轴突运输系统的状态。
In neurons, several intracellular cargoes are transported by motor proteins (kinesins) which walk on microtubules (MTs). However, kinesins can possibly unbind from the MTs before they reach their destinations. The unbound kinesins randomly diffuse in neurons until they bind to MTs. Then, they walk again along the MTs to continue their tasks. Kinesins repeat this cycle of motion until they transport their cargoes to the destinations. However, most previous models mainly focused on the motion of kinesins when they walk on MTs. Thus, a new model is required to encompass the various types of kinesin motion. We developed a comprehensive model and studied the long-range axonal transport of neurons using the model. To enhance reliability of the model, it was constructed based on multiphysics on kinesin motion (i.e., chemical kinetics, diffusion, fluid dynamics, nonlinear dynamics, and stochastic characteristics). Also, parameter values for kinesin motions are carefully obtained by comparing the model predictions and several experimental observations. The axonal transport can be degraded when a large number of binding sites on MTs are blocked by excessive tau proteins. By considering the interference between walking kinesins and tau molecules on MTs, effects of tau proteins on the axonal transport are studied. One of the meaningful predictions obtained from the model is that the velocity is not an effective metric to estimate the degradation of the transport because the decrease in velocity is not noticeable when the concentration of tau protein is not high. However, our model shows that the transport locally changes near tau molecules on MTs even when the change in the velocity is not significant. Thus, a statistical method is proposed to detect this local change effectively. The advantage of this method is that a value obtained from this method is highly sensitive to the concentration of tau protein. Another benefit of this method is that this highly sensitive value can be acquired with relatively low precision and low temporal resolution considering the time scale and length scale of the kinesin motion. This method can be used to estimate the condition of the axonal transport system.
DOI：
10.1021/issn.1520-6106
发表时间：
--
期刊：
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影响因子：
--
作者：
通讯作者：
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影响因子：
56.9
作者：
V. Gates;.. M. L. Ludwig-M.-L.-Ludwig-2273875465;J. A. Hartsuck;T. A. Steitz;H. Muirhead;J. C. Coppola;G. N. Reeke
通讯作者：
V. Gates;.. M. L. Ludwig-M.-L.-Ludwig-2273875465;J. A. Hartsuck;T. A. Steitz;H. Muirhead;J. C. Coppola;G. N. Reeke