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The promotion of neuronal maturation on soft substrates
Authors:Ana I. Teixeira  Shirin Ilkhanizadeh  Jens A. Wigenius  Joshua K. Duckworth  Olle Ingan?s  Ola Hermanson
Affiliation:1. Department of Neuroscience, Karolinska Institute, Stockholm SE 171 77, Sweden;2. Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics, Linköping University, Linköping SE 581 83, Sweden;1. Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH 44115, USA;2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;1. Institute of Physics, University Münster, Germany;2. Max-Planck-Institute for Molecular Biomedicine, Münster, Germany;1. Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore;2. Department of Biomedical Engineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117575, Singapore;3. Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 3 Research Link, Singapore 117602, Singapore;4. Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore;5. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore;1. Department of Biomedical Sciences, University of Padova, Viale Giuseppe Colombo 3, 35131 Padova, Italy;2. Department of Stomatology and Biotechnologies, University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;1. Laboratory of Stem Cells and Cell Reprogramming, Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea;2. School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea;3. Center for Biomicrosystems, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea;4. School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Republic of Korea;1. Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore;2. Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore;3. Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore;4. Department of Biomedical Engineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117575, Singapore;5. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore
Abstract:Microenvironmental mechanical properties of stem cell niches vary across tissues and developmental stages. Accumulating evidence suggests that matching substrate elasticity with in vivo tissue elasticity facilitates stem cell differentiation. However, it has not been established whether substrate elasticity can control the maturation stage of cells generated by stem cell differentiation. Here we show that soft substrates with elasticities commensurable to the elasticity of the brain promote the maturation of neural stem cell-derived neurons. In the absence of added growth factors, neurons differentiated on soft substrates displayed long neurites and presynaptic terminals, contrasting with the bipolar immature morphology of neurons differentiated on stiff substrates. Further, soft substrates supported an increase in astrocytic differentiation. However, stiffness cues could not override the dependency of astrocytic differentiation on Notch signaling. These results demonstrate that substrate elasticity per se can drive neuronal maturation thus defining a crucial parameter in neuronal differentiation of stem cells.
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