Matrix stiffness mechanosensing modulates the expression and distribution of transcription factors in Schwann cells

Rosso G, Wehner D, Schweitzer C, Sock E, Guck J, Shahin V, Möllmert S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Bioengineering & Translational Medicine Wiley

DOI: 10.1002/btm2.10257

Abstract

After peripheral nerve injury, mature Schwann cells (SCs) de-differentiate and undergo cell reprogramming to convert into a specialized cell repair phenotype that promotes nerve regeneration. Reprogramming of SCs into the repair phenotype is tightly controlled at the genome level and includes downregulation of pro-myelinating genes and activation of nerve repair-associated genes. Nerve injuries induce not only biochemical but also mechanical changes in the tissue architecture which impact SCs. Recently, we showed that SCs mechanically sense the stiffness of the extracellular matrix and that SC mechanosensitivity modulates their morphology and migratory behavior. Here, we explore the expression levels of key transcription factors and myelin-associated genes in SCs, and the outgrowth of primary dorsal root ganglion (DRG) neurites, in response to changes in the stiffness of generated matrices. The selected stiffness range matches the physiological conditions of both utilized cell types as determined in our previous investigations. We find that stiffer matrices induce upregulation of the expression of transcription factors Sox2, Oct6, and Krox20, and concomitantly reduce the expression of the repair-associated transcription factor c-Jun, suggesting a link between SC substrate mechanosensing and gene expression regulation. Likewise, DRG neurite outgrowth correlates with substrate stiffness. The remarkable intrinsic physiological plasticity of SCs, and the mechanosensitivity of SCs and neurites, may be exploited in the design of bioengineered scaffolds that promote nerve regeneration upon injury.

Authors with CRIS profile

Elisabeth Sock Lehrstuhl für Biochemie und Pathobiochemie Jochen Guck Lehrstuhl für Biologische Optomechanik Stephanie Möllmert

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE)

How to cite

APA:

Rosso, G., Wehner, D., Schweitzer, C., Sock, E., Guck, J., Shahin, V., & Möllmert, S. (2021). Matrix stiffness mechanosensing modulates the expression and distribution of transcription factors in Schwann cells. Bioengineering & Translational Medicine. https://doi.org/10.1002/btm2.10257

MLA:

Rosso, Gonzalo, et al. "Matrix stiffness mechanosensing modulates the expression and distribution of transcription factors in Schwann cells." Bioengineering & Translational Medicine (2021).

BibTeX: Download