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Stiff substrates enhance cultured neuronal network activity

The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into s...

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Autores principales: Zhang, Quan-You, Zhang, Yan-Yan, Xie, Jing, Li, Chen-Xu, Chen, Wei-Yi, Liu, Bai-Lin, Wu, Xiao-an, Li, Shu-Na, Huo, Bo, Jiang, Lin-Hua, Zhao, Hu-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147369/
https://www.ncbi.nlm.nih.gov/pubmed/25163607
http://dx.doi.org/10.1038/srep06215
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author Zhang, Quan-You
Zhang, Yan-Yan
Xie, Jing
Li, Chen-Xu
Chen, Wei-Yi
Liu, Bai-Lin
Wu, Xiao-an
Li, Shu-Na
Huo, Bo
Jiang, Lin-Hua
Zhao, Hu-Cheng
author_facet Zhang, Quan-You
Zhang, Yan-Yan
Xie, Jing
Li, Chen-Xu
Chen, Wei-Yi
Liu, Bai-Lin
Wu, Xiao-an
Li, Shu-Na
Huo, Bo
Jiang, Lin-Hua
Zhao, Hu-Cheng
author_sort Zhang, Quan-You
collection PubMed
description The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.
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spelling pubmed-41473692014-09-02 Stiff substrates enhance cultured neuronal network activity Zhang, Quan-You Zhang, Yan-Yan Xie, Jing Li, Chen-Xu Chen, Wei-Yi Liu, Bai-Lin Wu, Xiao-an Li, Shu-Na Huo, Bo Jiang, Lin-Hua Zhao, Hu-Cheng Sci Rep Article The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering. Nature Publishing Group 2014-08-28 /pmc/articles/PMC4147369/ /pubmed/25163607 http://dx.doi.org/10.1038/srep06215 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Zhang, Quan-You
Zhang, Yan-Yan
Xie, Jing
Li, Chen-Xu
Chen, Wei-Yi
Liu, Bai-Lin
Wu, Xiao-an
Li, Shu-Na
Huo, Bo
Jiang, Lin-Hua
Zhao, Hu-Cheng
Stiff substrates enhance cultured neuronal network activity
title Stiff substrates enhance cultured neuronal network activity
title_full Stiff substrates enhance cultured neuronal network activity
title_fullStr Stiff substrates enhance cultured neuronal network activity
title_full_unstemmed Stiff substrates enhance cultured neuronal network activity
title_short Stiff substrates enhance cultured neuronal network activity
title_sort stiff substrates enhance cultured neuronal network activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147369/
https://www.ncbi.nlm.nih.gov/pubmed/25163607
http://dx.doi.org/10.1038/srep06215
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