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PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells

Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defi...

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Autores principales: Chang, Fei-Chien, Tsao, Ching-Ting, Lin, Anqi, Zhang, Mengying, Levengood, Sheeny Lan, Zhang, Miqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004991/
https://www.ncbi.nlm.nih.gov/pubmed/27595012
http://dx.doi.org/10.3390/polym8040112
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author Chang, Fei-Chien
Tsao, Ching-Ting
Lin, Anqi
Zhang, Mengying
Levengood, Sheeny Lan
Zhang, Miqin
author_facet Chang, Fei-Chien
Tsao, Ching-Ting
Lin, Anqi
Zhang, Mengying
Levengood, Sheeny Lan
Zhang, Miqin
author_sort Chang, Fei-Chien
collection PubMed
description Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironment in vitro. We demonstrate a methoxypolyethylene glycol (mPEG)-modified chitosan hydrogel network where hydrogel stiffness can be easily modulated under physiological conditions by adjusting the degree of mPEG grafting onto chitosan (PEGylation). We show that the storage modulus of the hydrogel increases as PEGylation decreases and the gels exhibit instant self-recovery after deformation. Breast cancer cells cultured on the stiffest hydrogels adopt a more malignant phenotype with increased resistance to doxorubicin as compared with cells cultured on tissue culture polystyrene or Matrigel. This work demonstrates the utility of mPEG-modified chitosan hydrogel, with tunable mechanical properties, as an improved replacement of conventional culture system for in vitro characterization of breast cancer cell phenotype and evaluation of cancer therapies.
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spelling pubmed-50049912017-03-26 PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells Chang, Fei-Chien Tsao, Ching-Ting Lin, Anqi Zhang, Mengying Levengood, Sheeny Lan Zhang, Miqin Polymers (Basel) Article Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironment in vitro. We demonstrate a methoxypolyethylene glycol (mPEG)-modified chitosan hydrogel network where hydrogel stiffness can be easily modulated under physiological conditions by adjusting the degree of mPEG grafting onto chitosan (PEGylation). We show that the storage modulus of the hydrogel increases as PEGylation decreases and the gels exhibit instant self-recovery after deformation. Breast cancer cells cultured on the stiffest hydrogels adopt a more malignant phenotype with increased resistance to doxorubicin as compared with cells cultured on tissue culture polystyrene or Matrigel. This work demonstrates the utility of mPEG-modified chitosan hydrogel, with tunable mechanical properties, as an improved replacement of conventional culture system for in vitro characterization of breast cancer cell phenotype and evaluation of cancer therapies. MDPI 2016-03-26 /pmc/articles/PMC5004991/ /pubmed/27595012 http://dx.doi.org/10.3390/polym8040112 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Fei-Chien
Tsao, Ching-Ting
Lin, Anqi
Zhang, Mengying
Levengood, Sheeny Lan
Zhang, Miqin
PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title_full PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title_fullStr PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title_full_unstemmed PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title_short PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
title_sort peg-chitosan hydrogel with tunable stiffness for study of drug response of breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004991/
https://www.ncbi.nlm.nih.gov/pubmed/27595012
http://dx.doi.org/10.3390/polym8040112
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