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Article

Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases

1
Department of Chemical and Environmental Engineering, University of Cincinnati, Cincinnati, OH 45221, USA
2
Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA
3
Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Christophe Deroanne
Int. J. Mol. Sci. 2021, 22(9), 4821; https://doi.org/10.3390/ijms22094821
Received: 29 March 2021 / Revised: 27 April 2021 / Accepted: 28 April 2021 / Published: 1 May 2021
Schwann cells (SCs) are a highly plastic cell type capable of undergoing phenotypic changes following injury or disease. SCs are able to upregulate genes associated with nerve regeneration and ultimately achieve functional recovery. During the regeneration process, the extracellular matrix (ECM) and cell morphology play a cooperative, critical role in regulating SCs, and therefore highly impact nerve regeneration outcomes. However, the roles of the ECM and mechanotransduction relating to SC phenotype are largely unknown. Here, we describe the role that matrix stiffness and cell morphology play in SC phenotype specification via known mechanotransducers YAP/TAZ and RhoA. Using engineered microenvironments to precisely control ECM stiffness, cell shape, and cell spreading, we show that ECM stiffness and SC spreading downregulated SC regenerative associated proteins by the activation of RhoA and YAP/TAZ. Additionally, cell elongation promoted a distinct SC regenerative capacity by the upregulation of Rac1/MKK7/JNK, both necessary for the ECM and morphology changes found during nerve regeneration. These results confirm the role of ECM signaling in peripheral nerve regeneration as well as provide insight to the design of future biomaterials and cellular therapies for peripheral nerve regeneration. View Full-Text
Keywords: Schwann cell; mechanobiology; Rho GTPase; YAP/TAZ; extracellular matrix; peripheral nerve Schwann cell; mechanobiology; Rho GTPase; YAP/TAZ; extracellular matrix; peripheral nerve
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MDPI and ACS Style

Xu, Z.; Orkwis, J.A.; Harris, G.M. Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases. Int. J. Mol. Sci. 2021, 22, 4821. https://doi.org/10.3390/ijms22094821

AMA Style

Xu Z, Orkwis JA, Harris GM. Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases. International Journal of Molecular Sciences. 2021; 22(9):4821. https://doi.org/10.3390/ijms22094821

Chicago/Turabian Style

Xu, Zhenyuan, Jacob A. Orkwis, and Greg M. Harris. 2021. "Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases" International Journal of Molecular Sciences 22, no. 9: 4821. https://doi.org/10.3390/ijms22094821

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