Remote activation of the Wnt/β-catenin signalling pathway using functionalised magnetic particles

PloS One
Michael Rotherham, Alicia J El Haj

Abstract

Wnt signalling pathways play crucial roles in developmental biology, stem cell fate and tissue patterning and have become an attractive therapeutic target in the fields of tissue engineering and regenerative medicine. Wnt signalling has also been shown to play a role in human Mesenchymal Stem Cell (hMSC) fate, which have shown potential as a cell therapy in bone and cartilage tissue engineering. Previous work has shown that biocompatible magnetic nanoparticles (MNP) can be used to stimulate specific mechanosensitive membrane receptors and ion channels in vitro and in vivo. Using this strategy, we determined the effects of mechano-stimulation of the Wnt Frizzled receptor on Wnt pathway activation in hMSC. Frizzled receptors were tagged using anti-Frizzled functionalised MNP (Fz-MNP). A commercially available oscillating magnetic bioreactor (MICA Biosystems) was used to mechanically stimulate Frizzled receptors remotely. Our results demonstrate that Fz-MNP can activate Wnt/β-catenin signalling at key checkpoints in the signalling pathway. Immunocytochemistry indicated nuclear localisation of the Wnt intracellular messenger β-catenin after treatment with Fz-MNP. A Wnt signalling TCF/LEF responsive luciferase reporter transfected i...Continue Reading

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Oct 21, 2015·The International Journal of Biochemistry & Cell Biology·Hareklea MarkidesAlicia J El Haj
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Aug 8, 2021·Cells·Hareklea MarkidesAlicia J El Haj
Nov 7, 2021·Small·Miriam FilippiRobert K Katzschmann

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Methods Mentioned

BETA
PCR

Software Mentioned

tab
ImageJ
NIS elements
MxPro
Mini
Gen5

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