Skip to main content

Research Repository

Advanced Search

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics.

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics. Thumbnail


Abstract

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/ß-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics.

Acceptance Date Aug 30, 2022
Publication Date Sep 5, 2022
Publicly Available Date Mar 29, 2024
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
DOI https://doi.org/10.3390/ijms231710164
Publisher URL https://www.mdpi.com/1422-0067/23/17/10164

Files




Downloadable Citations