Matrix Stiffness Modulates Mesenchymal Stem Cell Sensitivity to Geometric Asymmetry Signals
Human stem cells hold significant potential for the treatment of various diseases. However, their use as a therapy is hampered because of limited understanding of the mechanisms by which they respond to environmental stimuli. Efforts to understand extracellular biophysical cues have demonstrated the critical roles of geometrical and mechanical signals in determining the fate of stem cells. The goal of this study was to explore the interplay between cell polarity and matrix stiffness in stem cell lineage specification. We hypothesize that confining cells to asymmetric extracellular matrix islands will impart polarity at a single-cell level and will interact with mechanical signals to define the lineage of stem cells. To test these hypotheses, we employed microcontact printing to create patterned symmetric and asymmetric hydrogel islands of soft and hard surface stiffness. Human mesenchymal stem cells (hMSCs) were confined to these islands at the single-cell level and given the ability to differentiate along adipogenic or osteogenic routes. Our results demonstrated that cell polarity defines the lineage specification of hMSCs only on islands with low stiffness. Insight gained from this study provides a rational basis for designing stem cell cultures to enhance tissue engineering and regenerative medicine strategies.
KeywordsCell polarity Matrix elasticity Micropatterning Mesenchymal stem cells
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number AR063338. We would like to thank Dr. Tarek Shazly and Will Torres for assisting us with the use of the Electroforce 3200.
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