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{Kit-Anan:2021:1758-5090/abce0a,
author = {Kit-Anan, W and Mazo, M and Wang, BX and Leonardo, V and Pence, I and Gopal, S and Gelmi, A and Becce, M and Chiappini, C and Harding, SE and Terracciano, C and Stevens, M},
doi = {1758-5090/abce0a},
journal = {Biofabrication},
pages = {1--16},
title = {Multiplexing physical stimulation on single human induced pluripotent stem cell-derived cardiomyocytes for phenotype modulation},
url = {http://dx.doi.org/10.1088/1758-5090/abce0a},
volume = {13},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Traditional in vitro bioengineering approaches whereby only individual biophysical cues are manipulated at any one time are highly inefficient, falling short when recapitulating the complexity of the cardiac environment. Multiple biophysical cues are present in the native myocardial niche and are essential during development, as well as in maintenance of adult cardiomyocyte (CM) phenotype in both health and disease. This study establishes a novel biofabrication workflow to study and manipulate hiPSC-CMs and to understand how these cells respond to a multiplexed biophysical environment, namely microscopic topography (3D shape resembling that of adult CM) and substrate stiffness, at a single cell level. Silicon masters were fabricated and developed to generate pillars of the desired 3D shapes, which would be used to mould the designed microwell arrays into a hydrogel. Polyacrylamide was modified with the incorporation of acrylic acid to provide a carboxylic group conjugation site for adhesion motifs, without comprising its capacity to modulate the stiffness. In this manner, individual parameters can be finely tuned independently within the hydrogel: the dimension of 3D shaped microwell and its stiffness. The design allows the platform to isolate single hiPSC-CMs to study solely biophysical cues in an absence of cell-cell physical interaction. Under physiologic-like physical conditions (3D shape resembling that of adult CM and 9.83 kPa substrate stiffness), isolated single hiPSC-CMs exhibit increased Cx-43 density, cell  Peer reviewed version of the manuscript published in final form at Biofabrication (2020). membrane stiffness and calcium transient amplitude; co-expression of the subpopulation-related MYL2- MYL7 proteins; while displaying higher anisotropism in comparison to pathologic-like conditions (flat surface and 112 kPa substrate stiffness). This demonstrates that supplying a physiological or pathological microenvironment to an isolated single hiPSC-CM in absen
AU  - Kit-Anan,W
AU  - Mazo,M
AU  - Wang,BX
AU  - Leonardo,V
AU  - Pence,I
AU  - Gopal,S
AU  - Gelmi,A
AU  - Becce,M
AU  - Chiappini,C
AU  - Harding,SE
AU  - Terracciano,C
AU  - Stevens,M
DO  - 1758-5090/abce0a
EP  - 16
PY  - 2021///
SN  - 1758-5082
SP  - 1
TI  - Multiplexing physical stimulation on single human induced pluripotent stem cell-derived cardiomyocytes for phenotype modulation
T2  - Biofabrication
UR  - http://dx.doi.org/10.1088/1758-5090/abce0a
UR  - https://iopscience.iop.org/article/10.1088/1758-5090/abce0a/meta
UR  - http://hdl.handle.net/10044/1/85025
VL  - 13
ER  -
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