Long-range directional growth of neurites induced by magnetic forces

Nahar, Tasmin; Gates, Monte; Secret, Emilie; Siaugue, Jean-Michel; Fresnais, Jerome; Rotherham, Michael; Fuller, Heidi R; Brown, Sharon J; El Haj, Alicia J; Telling, Neil D

Abstract

The ability to control the growth and orientation of neurites over long distances has significant implications for regenerative therapies and the development of physiologically relevant brain tissue models. In this study, the forces generated on magnetic nanoparticles internalised within intracellular endosomes are used to direct the orientation of neuronal outgrowth in cell cultures. Following differentiation, neurite orientation was observed after 3 days application of magnetic forces to human neuroblastoma (SH-SY5Y) cells, and after 4 days application to rat cortical primary neurons. The direction of neurite outgrowth was quantified using a 2D Fourier transform analysis, showing agreement with the derived magnetic force vectors. Orientation control was found to be effective over areas >1cm2 using modest forces of ∼10 fN per endosome, apparently limited only by the local confluence of the cells. A bioinformatics analysis of protein expression in cells exposed to magnetic forces revealed changes to cell signaling and metabolic pathways resulting in enhanced carbohydrate metabolism, as well as the perturbation of processes related to cellular organisation and proliferation. Additionally, in cell culture regions where the measured force vectors converged, large (∼100 µm) SH-SY5Y neuroclusters loaded with nanoparticles were found, connected by unusually thick linear neurite fibres. This could suggest a magnetically driven enhancement of neurocluster growth, with the clusters themselves contributing to the local forces that direct outgrowth. Such structures, which have not been previously observed, could provide new insights into the development and possible enhancement of neural circuitry.

Citation

Nahar, T., Gates, M., Secret, E., Siaugue, J.-M., Fresnais, J., Rotherham, M., …Telling, N. D. (in press). Long-range directional growth of neurites induced by magnetic forces. Acta biomaterialia, https://doi.org/10.1016/j.actbio.2024.12.057

• Journal Article Type: Article
• Acceptance Date: Dec 26, 2024
• Online Publication Date: Jan 2, 2025
• Deposit Date: Jan 10, 2025
• Publicly Available Date: Jan 14, 2025
• Journal: Acta Biomaterialia
• Print ISSN: 1742-7061
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.actbio.2024.12.057
• Keywords: Magnetogenetics, Neuroregeneration, Magnetic forces, Magnetic nanoparticles, Neurite growth
• Public URL: https://keele-repository.worktribe.com/output/1045773
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1742706124007773?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Long-range directional growth of neurites induced by magnetic forces; Journal Title: Acta Biomaterialia; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.actbio.2024.12.057; Content Type: article; Copyright: © 2025 The Authors. Published by Elsevier Inc. on behalf of Acta Materialia Inc.