Imperial College London
Alternate

Professor Molly Stevens

Faculty of Engineering, Department of Materials

Professor of Biomedical Materials and Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hsu:2022:10.1021/acsami.2c01996,
author = {Hsu, CC and Serio, A and Gopal, S and Gelmi, A and Chiappini, C and Desai, R and Stevens, M},
doi = {10.1021/acsami.2c01996},
journal = {ACS Applied Materials and Interfaces},
title = {Biophysical regulations of epigenetic state and notch signalling in neural development using microgroove substrates},
url = {http://dx.doi.org/10.1021/acsami.2c01996},
volume = {14},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A number of studies have recently shown how surface topography can alter behaviour and differentiation patterns of different types of stem cells. Although the exact mechanisms and molecular pathways involved remain unclear, a consistent portion of the literature points to epigenetic changes induced by nuclear remodelling. In this study, we investigate the behaviour of clinically relevant neural populations derived from human pluripotent stem cells when cultured on polydimethylsiloxane microgrooves (3 μm- and 10 μm-depth grooves), to investigate what mechanisms are responsible for their differentiation capacity and functional behaviour. Our results show that microgrooves enhance cell alignment, modify nuclear geometry and significantly increase cellular stiffness, which we were able to measure at high resolution with a combination of light and electron microscopy, scanning ion conductance microscopy (SICM) and atomic force microscopy (AFM) coupled with quantitative image analysis. The microgrooves promoted significant changes in the epigenetic landscape, as revealed by the expression of key histone modification markers. The main behavioural change of neural stem cells on microgrooves was an increase of neuronal differentiation under basal conditions on the microgrooves. Through measurements of cleaved Notch1 levels, we found that microgrooves downregulate Notch signalling. We in fact propose that microgroovetopography affects the differentiation potential of neural stem cells by indirectly altering Notch signalling through geometric segregation and that this mechanism in parallel with topography-dependent epigenetic modulations acts in concert to enhance stem cell neuronal differentiation.
AU  - Hsu,CC
AU  - Serio,A
AU  - Gopal,S
AU  - Gelmi,A
AU  - Chiappini,C
AU  - Desai,R
AU  - Stevens,M
DO  - 10.1021/acsami.2c01996
PY  - 2022///
SN  - 1944-8244
TI  - Biophysical regulations of epigenetic state and notch signalling in neural development using microgroove substrates
T2  - ACS Applied Materials and Interfaces
UR  - http://dx.doi.org/10.1021/acsami.2c01996
UR  - https://pubs.acs.org/doi/10.1021/acsami.2c01996
UR  - http://hdl.handle.net/10044/1/98278
VL  - 14
ER  -
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