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Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification

Li, YM; Ji, Y; Meng, YX; Kim, YJ; Lee, H; Kurian, AG; Park, JH; ... Lee, JH; + view all (2024) Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification. Advanced Science p. 2400586. 10.1002/advs.202400586. Green open access

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Abstract

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

Type: Article
Title: Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/advs.202400586
Publisher version: https://doi.org/10.1002/advs.202400586
Language: English
Additional information: Copyright © 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: calcium signaling, electrical conductivity, epigenetic change, neural lineage specification
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute > Biomaterials and Tissue Eng
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10194710
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