论文标题

沿着不均匀微管的运动蛋白传输

Motor protein transport along inhomogeneous microtubules

论文作者

Ryan, Shawn D., McCarthy, Zachary, Potomkin, Mykhailo

论文摘要

许多细胞过程都依赖于细胞向核传输材料的能力。由许多微管和肌动蛋白丝组成的网络是该运输的关键。最近,细胞内转运的抑制与神经退行性疾病有关,例如阿尔茨海默氏病和肌萎缩性侧面硬化症(ALS)。此外,微管可能包含所谓的缺陷区域,由于其他电动机和微管相关蛋白的积累,运动蛋白速度降低。在这项工作中,我们提出了一个新的数学模型,该模型描述了在微管上运动蛋白的运动,该模型融合了一个有缺陷的区域。我们采用从第一个原理晶格模型得出的平均场方法来研究运动蛋白动力学和密度曲线。特别是,给定一组模型参数,我们获得了沿给定微管的平衡密度曲线的闭合形式表达式。然后,我们使用离散模型和蒙特卡洛模拟的数学分析来验证分析结果。这项工作将有助于对不均匀微管的基本理解,从而提供对微观相互作用的见解,这可能导致神经退行性疾病的发作。我们的不均匀微管的结果与先前研究均匀案例的工作一致。

Many cellular processes rely on the cell's ability to transport material to and from the nucleus. Networks consisting of many microtubules and actin filaments are key to this transport. Recently, the inhibition of intracellular transport has been implicated in neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS). Furthermore, microtubules may contain so-called defective regions where motor protein velocity is reduced due to accumulation of other motors and microtubule associated proteins. In this work, we propose a new mathematical model describing the motion of motor proteins on microtubules which incorporate a defective region. We take a mean-field approach derived from a first principle lattice model to study motor protein dynamics and density profiles. In particular, given a set of model parameters we obtain a closed-form expression for the equilibrium density profile along a given microtubule. We then verify the analytic results using mathematical analysis on the discrete model and Monte Carlo simulations. This work will contribute to the fundamental understanding of inhomogeneous microtubules providing insight into microscopic interactions that may result in the onset of neurodegenerative diseases. Our results for inhomogeneous microtubules are consistent with prior work studying the homogeneous case.

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