Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation

Abstract In vivo, multiple biophysical cues provided by highly ordered connective tissues of the extracellular matrix regulate skeletal muscle cells to align in parallel with one another. However, in routine in vitro cell culture environments, these key factors are often missing, which leads to chan...

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Autores principales: Cong Wu, Chriss S. M. Chin, Qingyun Huang, Ho-Yin Chan, Xinge Yu, Vellaisamy A. L. Roy, Wen J. Li
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Publicado: Nature Publishing Group 2021
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spelling oai:doaj.org-article:69130cdb993a4c5ba283aa54ee50b7b62021-11-07T12:11:58ZRapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation10.1038/s41378-021-00316-42055-7434https://doaj.org/article/69130cdb993a4c5ba283aa54ee50b7b62021-11-01T00:00:00Zhttps://doi.org/10.1038/s41378-021-00316-4https://doaj.org/toc/2055-7434Abstract In vivo, multiple biophysical cues provided by highly ordered connective tissues of the extracellular matrix regulate skeletal muscle cells to align in parallel with one another. However, in routine in vitro cell culture environments, these key factors are often missing, which leads to changes in cell behavior. Here, we present a simple strategy for using optical media discs with nanogrooves and other polymer-based substrates nanomolded from the discs to directly culture muscle cells to study their response to the effect of biophysical cues such as nanotopography and substrate stiffness. We extend the range of study of biophysical cues for myoblasts by showing that they can sense ripple sizes as small as a 100 nm width and a 20 nm depth for myotube alignment, which has not been reported previously. The results revealed that nanotopography and substrate stiffness regulated myoblast proliferation and morphology independently, with nanotopographical cues showing a higher effect. These biophysical cues also worked synergistically, and their individual effects on cells were additive; i.e., by comparing cells grown on different polymer-based substrates (with and without nanogrooves), the cell proliferation rate could be reduced by as much as ~29%, and the elongation rate could be increased as much as ~116%. Moreover, during myogenesis, muscle cells actively responded to nanotopography and consistently showed increases in fusion and maturation indices of ~28% and ~21%, respectively. Finally, under electrical stimulation, the contraction amplitude of well-aligned myotubes was found to be almost 3 times greater than that for the cells on a smooth surface, regardless of the substrate stiffness.Cong WuChriss S. M. ChinQingyun HuangHo-Yin ChanXinge YuVellaisamy A. L. RoyWen J. LiNature Publishing GrouparticleTechnologyTEngineering (General). Civil engineering (General)TA1-2040ENMicrosystems & Nanoengineering, Vol 7, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Technology
T
Engineering (General). Civil engineering (General)
TA1-2040
spellingShingle Technology
T
Engineering (General). Civil engineering (General)
TA1-2040
Cong Wu
Chriss S. M. Chin
Qingyun Huang
Ho-Yin Chan
Xinge Yu
Vellaisamy A. L. Roy
Wen J. Li
Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
description Abstract In vivo, multiple biophysical cues provided by highly ordered connective tissues of the extracellular matrix regulate skeletal muscle cells to align in parallel with one another. However, in routine in vitro cell culture environments, these key factors are often missing, which leads to changes in cell behavior. Here, we present a simple strategy for using optical media discs with nanogrooves and other polymer-based substrates nanomolded from the discs to directly culture muscle cells to study their response to the effect of biophysical cues such as nanotopography and substrate stiffness. We extend the range of study of biophysical cues for myoblasts by showing that they can sense ripple sizes as small as a 100 nm width and a 20 nm depth for myotube alignment, which has not been reported previously. The results revealed that nanotopography and substrate stiffness regulated myoblast proliferation and morphology independently, with nanotopographical cues showing a higher effect. These biophysical cues also worked synergistically, and their individual effects on cells were additive; i.e., by comparing cells grown on different polymer-based substrates (with and without nanogrooves), the cell proliferation rate could be reduced by as much as ~29%, and the elongation rate could be increased as much as ~116%. Moreover, during myogenesis, muscle cells actively responded to nanotopography and consistently showed increases in fusion and maturation indices of ~28% and ~21%, respectively. Finally, under electrical stimulation, the contraction amplitude of well-aligned myotubes was found to be almost 3 times greater than that for the cells on a smooth surface, regardless of the substrate stiffness.
format article
author Cong Wu
Chriss S. M. Chin
Qingyun Huang
Ho-Yin Chan
Xinge Yu
Vellaisamy A. L. Roy
Wen J. Li
author_facet Cong Wu
Chriss S. M. Chin
Qingyun Huang
Ho-Yin Chan
Xinge Yu
Vellaisamy A. L. Roy
Wen J. Li
author_sort Cong Wu
title Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
title_short Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
title_full Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
title_fullStr Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
title_full_unstemmed Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
title_sort rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/69130cdb993a4c5ba283aa54ee50b7b6
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