Induction of notch signaling by immobilization of jagged-1 on self-assembled monolayers

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Raquel M. Gonçalves (Author) Other; M. Cristina L. Martins (Author) FEUP; Graça Almeida-Porada (Author) FEUP; Mário A. Barbosa (Author) FEUP

Journal

Title: Biomaterials

Vol. 30 No. 36

Pages: 6879-6887

ISSN: 0142-9612

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 26 Citations

ISI Web of Science

Scopus - 28 Citations

COMPENDEX

INSPEC

Scientific classification

FOS: Medical and Health sciences > Medical biotechnology

CORDIS: Technological sciences > Engineering > Biomaterial engineering

Other information

Authenticus ID: P-003-DR3

DOI: 10.1016/j.biomaterials.2009.09.010

Abstract (EN): Notch signaling is a key mechanism during mammal development and stem cell regulation. This study aims to target and control Notch signaling by ligands immobilization using self-assembled monolayers (SAMs) as model surfaces. Non-fouling substrates were prepared by immersion of gold substrates in (1-Mercapto-11-undecyl)tetra(ethylene glycol) thiol solutions. These surfaces were activated with N,N′-carbonyldiimidazole (CDI) at different concentrations (0, 0.03, 0.3, 3 and 30 mg/ml) and an anti-human IgG, Fc specific fragment antibody (Ab) was covalently bound to EG4-SAMs to guarantee the correct exposure of the Notch ligand Jagged-1/Fc chimera (Jag-1). The presence of Ab and Jag-1 was confirmed by radiolabeling, X-ray photoelectron spectroscopy (XPS), ellipsometry and ELISA. The biological activity of Jag-1-Ab-SAMs was assessed by real-time PCR for Hes-1 family gene expression, a Notch pathway target gene, in HL-60 cell line. Results have shown an increase of the amount of immobilized Ab with increasing surface activator concentrations. Jag-1 concentration also increases with Ab concentration. Interestingly, a higher Jagged-1 exposure and fold increase in Hes-1 expression were obtained for surfaces activated with the lowest concentration of CDI (0.03 mg/ml). These results illustrate the great importance of ligands orientation and exposure, when compared with density. This investigation brings new insights into Notch signaling mechanisms. In particular, Jag-1-Ab-SAMs have shown to be adequate model surfaces to study Notch pathway activation and may provide a basis to develop new interfaces in biomaterials to control Notch mechanism in different cell systems.

Language: English

Type (Professor's evaluation): Scientific