Modeling material transport regulation and traffic jam in neurons using PDE-constrained optimization

TL;DR

This paper introduces a PDE-constrained optimization model to simulate and analyze material transport regulation and traffic jams in neurons, accounting for complex geometries and microtubule structures.

Contribution

It develops a novel PDE-based optimization framework using isogeometric analysis to model neuronal transport and traffic jams, advancing understanding of transport regulation in neurons.

Findings

Model successfully simulates traffic jams caused by microtubule disruptions.

Geometry and microtubule structure significantly influence transport efficiency.

The approach explains traffic jam formation in abnormal neurons.

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 complex geometries of neurons. The transport is controlled to avoid traffic jam of materials by minimizing a pre-defined 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 isogeometric analysis (IGA). 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 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 neuron.