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-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironmentin 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 forin vitrocharacterization of breast cancer cell phenotype and evaluation of cancer therapies.
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Fei-Chien
FC
Chang
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Ching-Ting
CT
Tsao
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Anqi
A
Lin
Department of Molecular Engineering and Science Institute, University of Washington, Seattle, Washington 98195, USA.
Mengying
M
Zhang
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Sheeny Lan
SL
Levengood
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Miqin
M
Zhang
chitosan; extracellular matrix; hydrogel; modulus; stiffness; tunable