%0 Journal Article
%T Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.
%A Li YM
%A Ji Y
%A Meng YX
%A Kim YJ
%A Lee H
%A Kurian AG
%A Park JH
%A Yoon JY
%A Knowles JC
%A Choi Y
%A Kim YS
%A Yoon BE
%A Singh RK
%A Lee HH
%A Kim HW
%A Lee JH
%J Adv Sci (Weinh)
%V 0
%N 0
%D 2024 Jul 10
%M 38984490
%F 17.521
%R 10.1002/advs.202400586
%X 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.