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Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt\/\u03b2-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.<\/jats:p>","DOI":"10.3390\/ijms231710164","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5642-8300","authenticated-orcid":false,"given":"Bin","family":"Hu","sequence":"first","affiliation":[{"name":"School of Pharmacy and Bioengineering, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire ST4 7QB, UK"},{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-7681","authenticated-orcid":false,"given":"Michael","family":"Rotherham","sequence":"additional","affiliation":[{"name":"Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Heritage Building, Mindelsohn Way, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Farrow","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire ST4 7QB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4135-9733","authenticated-orcid":false,"given":"Paul","family":"Roach","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire ST4 7QB, UK"},{"name":"Department of Chemistry, Loughborough University, Leicestershire, Loughborough LE11 3TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Dobson","sequence":"additional","affiliation":[{"name":"J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia J.","family":"El Haj","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire ST4 7QB, UK"},{"name":"Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Heritage Building, Mindelsohn Way, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/\u03b2-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.cell.2012.05.002","article-title":"Wnt signaling through inhibition of \u03b2-catenin degradation in an intact Axin1 complex","volume":"149","author":"Li","year":"2012","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/35083601","article-title":"Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains","volume":"412","author":"Dann","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1073\/pnas.1103102108","article-title":"Winning WNT: Race to Wnt signaling inhibitors","volume":"108","author":"Watanabe","year":"2011","journal-title":"Proc. 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