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Published on: August 8, 2017
Mechanical Cell Reprogramming on Tissue-Mimicking Hydrogels for Cancer Cell Transdifferentiation
Xueqing Ren1, Yachao Wang2, Mengcheng Lei1
1Key Laboratory of Molecular Biophysics of MOE and Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology-Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Tissue matrix mechanics influence cell behavior and health. This study demonstrates that mechanical reprogramming using tissue-mimicking hydrogels can reprogram cells, promoting stemness and potentially treating diseases like cancer.
Area of Science:
- Biomaterials Science
- Cell Biology
- Regenerative Medicine
Background:
- Disrupted tissue matrix mechanics are linked to diseases like cancer and neurodegeneration.
- Aging tissue matrix loses integrity and alters biophysical properties.
- The role of matrix mechanical properties in regulating cell health and function is largely unknown.
Purpose of the Study:
- To investigate if cells exhibit reprogrammed behaviors when cultured in a tissue-mimicking mechanical microenvironment.
- To explore the potential of mechanical reprogramming for regenerative medicine and cancer therapy.
Main Methods:
- Constructed a tissue-mimicking hydrogel with viscoelastic and nonlinear elastic components.
- Cultured fibroblasts on the hydrogel, observing aggregate formation and gene expression.
- Applied mechanical reprogramming to non-small-lung cancer cells.
Main Results:
- Fibroblasts formed mesenchymal aggregates with elevated stemness genes and enhanced differentiation potential.
- Mesenchymal aggregate formation was driven by collagen network reorganization via cell contraction.
- Mechanical reprogramming induced adipogenic transdifferentiation in lung cancer cells, reversing epithelial-to-mesenchymal transition markers and suppressing oncogenes.
Conclusions:
- Cellular behaviors can be reprogrammed by mechanical microenvironments.
- Mechanical reprogramming on tissue-mimicking hydrogels shows promise for regenerative medicine and cancer treatment.
- This approach offers a novel strategy for disease treatment by modulating cellular mechanical properties.
