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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Gonzalo Rosso - (Author)
  • Daniel Wehner - (Author)
  • Christine Schweitzer - (Author)
  • Stephanie Möllmert - (Author)
  • Elisabeth Sock - (Author)
  • Jochen Guck - , Chair of Cellular Machines (Author)
  • Victor Shahin - (Author)

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.

Details

Original languageEnglish
Article numbere10257
Number of pages8
Journal Bioengineering & translational medicine : official journal of the American Institute of Chemical Engineers (AIChE)
Volume7
Issue number1
Publication statusPublished - Jan 2022
Peer-reviewedYes

External IDs

WOS 000697498500001

Keywords

Keywords

  • Schwann cell, Cell plasticity, Extracellular matrix stiffness, Mechanosensing, Nerve regeneration, Neuron