Modeling intracellular transport and traffic jam in 3D neurons using PDE-constrained optimization

IF 1.5 4区 工程技术 Q3 MECHANICS
Angran Li, Y. Zhang
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引用次数: 5

Abstract

The intracellular transport process plays an important role in delivering essential materials throughout branched geometries of neurons for their survival and function. Many neurodegenerative diseases have been associated with the disruption of transport. Therefore, it is essential to study how neurons control the transport process to localize materials to necessary locations. Here, we develop a novel optimization model to simulate the traffic regulation mechanism of material transport in three-dimensional complex geometries of neurons. The transport is controlled to avoid traffic jams of materials by minimizing a predefined objective function. The optimization subjects to a set of partial differential equation (PDE) constraints that describe the material transport process based on a macroscopic molecular-motor-assisted transport model of intracellular particles. The proposed PDE-constrained optimization model is solved in complex tree structures by using the isogeometric analysis. Different simulation parameters are used to introduce traffic jams and study how neurons handle the transport issue. Specifically, we successfully model and explain the traffic jam caused by the reduced number of microtubules (MTs) and MT swirls. In summary, our model effectively simulates the material transport process in healthy neurons and also explains the formation of a traffic jam in abnormal neurons. Our results demonstrate that both geometry and MT structure play important roles in achieving an optimal transport process in neurons.
基于pde约束优化的三维神经元细胞内运输和交通阻塞建模
细胞内转运过程在神经元分支几何结构中传递必需物质以维持其存活和功能方面起着重要作用。许多神经退行性疾病都与转运受阻有关。因此,研究神经元如何控制转运过程以将物质定位到需要的位置是非常必要的。在此,我们建立了一个新的优化模型来模拟神经元三维复杂几何结构中物质运输的交通调节机制。通过最小化预定义的目标函数来控制运输以避免物料的交通堵塞。基于细胞内颗粒的宏观分子-马达辅助运输模型,优化过程受一组描述物质运输过程的偏微分方程(PDE)约束。提出的pde约束优化模型采用等距分析方法求解复杂树形结构。采用不同的仿真参数来引入交通阻塞,研究神经元如何处理交通问题。具体来说,我们成功地模拟和解释了由微管(MT)和MT漩涡数量减少引起的交通堵塞。综上所述,我们的模型有效地模拟了健康神经元中的物质运输过程,也解释了异常神经元中交通堵塞的形成。我们的研究结果表明,几何和MT结构在实现神经元的最佳运输过程中起着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Mechanics
Journal of Mechanics 物理-力学
CiteScore
3.20
自引率
11.80%
发文量
20
审稿时长
6 months
期刊介绍: The objective of the Journal of Mechanics is to provide an international forum to foster exchange of ideas among mechanics communities in different parts of world. The Journal of Mechanics publishes original research in all fields of theoretical and applied mechanics. The Journal especially welcomes papers that are related to recent technological advances. The contributions, which may be analytical, experimental or numerical, should be of significance to the progress of mechanics. Papers which are merely illustrations of established principles and procedures will generally not be accepted. Reports that are of technical interest are published as short articles. Review articles are published only by invitation.
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