Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway

Cell Prolif. 2018 Dec;51(6):e12503. doi: 10.1111/cpr.12503. Epub 2018 Aug 9.

Abstract

Objectives: The main purpose of current study was to explore the effects of tetrahedral DNA nanostructures (TDNs) on neuroectodermal (NE-4C) stem cells migration and unveil the potential mechanisms.

Materials and methods: The successfully self-assembled TDNs were also determined by dynamic light scattering (DLS). A bidirectional wound-healing assay and transwell chamber assay were employed to test the migrating behaviour of NE-4C stem cells cultured under different conditions.

Results: Through an in vitro study, we found that stem cells could internalize TDNs quickly, and the cells' parallel and vertical migration was promoted effectively. Besides, the effects of TDNs were found being exerted by upregulating the gene and protein expression levels of RhoA, Rock2 and Vinculin, indicating that the RHOA/ROCK2 pathway was activated by the TDNs during the cell migration.

Conclusions: In conclusion, TDNs could enter NSCs without the aid of other transfection reagents in large amounts, whereas only small amounts of ssDNA could enter the cells. TDNs taken up by NSCs activated the RHOA/ROCK2 signalling pathway, which had effects on the relevant genes and proteins expression, eventually promoting the migration of NE-4C stem cells. These findings suggested that TDNs have great potential in application for the repair and regeneration of neural tissue.

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • DNA / pharmacology*
  • Nanostructures
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects
  • Signal Transduction / drug effects
  • Transfection / methods
  • rho-Associated Kinases / drug effects*
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / drug effects*
  • rhoA GTP-Binding Protein / genetics

Substances

  • DNA
  • Rock2 protein, mouse
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein