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微管蛋白驱动的轴突生长的高效模拟

Efficient simulations of tubulin-driven axonal growth.

作者信息

Diehl Stefan, Henningsson Erik, Heyden Anders

机构信息

Centre for Mathematical Sciences, Lund University, P.O. Box 118, 221 00, Lund, Sweden.

出版信息

J Comput Neurosci. 2016 Aug;41(1):45-63. doi: 10.1007/s10827-016-0604-x. Epub 2016 Apr 28.

Abstract

This work concerns efficient and reliable numerical simulations of the dynamic behaviour of a moving-boundary model for tubulin-driven axonal growth. The model is nonlinear and consists of a coupled set of a partial differential equation (PDE) and two ordinary differential equations. The PDE is defined on a computational domain with a moving boundary, which is part of the solution. Numerical simulations based on standard explicit time-stepping methods are too time consuming due to the small time steps required for numerical stability. On the other hand standard implicit schemes are too complex due to the nonlinear equations that needs to be solved in each step. Instead, we propose to use the Peaceman-Rachford splitting scheme combined with temporal and spatial scalings of the model. Simulations based on this scheme have shown to be efficient, accurate, and reliable which makes it possible to evaluate the model, e.g. its dependency on biological and physical model parameters. These evaluations show among other things that the initial axon growth is very fast, that the active transport is the dominant reason over diffusion for the growth velocity, and that the polymerization rate in the growth cone does not affect the final axon length.

摘要

这项工作涉及对微管驱动的轴突生长移动边界模型动态行为的高效且可靠的数值模拟。该模型是非线性的,由一组耦合的偏微分方程(PDE)和两个常微分方程组成。PDE在具有移动边界的计算域上定义,移动边界是解的一部分。基于标准显式时间步长方法的数值模拟由于数值稳定性所需的小时间步长而非常耗时。另一方面,标准隐式格式由于在每一步都需要求解非线性方程而过于复杂。相反,我们建议使用Peaceman-Rachford分裂格式并结合模型的时间和空间尺度变换。基于该格式的模拟已证明是高效、准确且可靠的,这使得评估该模型成为可能,例如评估其对生物和物理模型参数的依赖性。这些评估表明,除其他外,初始轴突生长非常快,主动运输是生长速度超过扩散的主要原因,并且生长锥中的聚合速率不影响最终轴突长度。

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