Chang Fei-Chien, Tsao Ching-Ting, Lin Anqi, Zhang Mengying, Levengood Sheeny Lan, Zhang Miqin
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Department of Molecular Engineering and Science Institute, University of Washington, Seattle, Washington 98195, USA.
Polymers (Basel). 2016;8(4). doi: 10.3390/polym8040112. Epub 2016 Mar 26.
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 . 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 characterization of breast cancer cell phenotype and evaluation of cancer therapies.
细胞外基质的力学性能对锚定依赖性细胞的行为有着深远影响。然而，决定基质硬度对细胞行为影响的机制仍不清楚。因此，开发和制造具有明确硬度的合成基质对于研究细胞与其生物物理微环境的相互作用具有重要价值。我们展示了一种甲氧基聚乙二醇（mPEG）修饰的壳聚糖水凝胶网络，通过调节mPEG接枝到壳聚糖上的程度（聚乙二醇化），可以在生理条件下轻松调节水凝胶的硬度。我们发现，随着聚乙二醇化程度降低，水凝胶的储能模量增加，并且凝胶在变形后表现出即时自我恢复能力。与在组织培养聚苯乙烯或基质胶上培养的细胞相比，在最硬水凝胶上培养的乳腺癌细胞呈现出更具恶性的表型，对阿霉素的抗性增强。这项工作证明了具有可调力学性能的mPEG修饰壳聚糖水凝胶作为传统培养系统的改进替代品，用于表征乳腺癌细胞表型和评估癌症治疗方法的实用性。
