Regulation of integrin adhesions by varying the density of substrate-bound epidermal growth factor

• Verfasst von: Shahal, Tamar [VerfasserIn]
• Verfasst von: Spatz, Joachim P. [VerfasserIn]
• Titel: Regulation of integrin adhesions by varying the density of substrate-bound epidermal growth factor
• Verf.angabe: Tamar Shahal, Benjamin Geiger, Iain E. Dunlop, Joachim P. Spatz
• E-Jahr: 2012
• Jahr: 3 March 2012
• Umfang: 11 S.
• Fussnoten: Gesehen am 23.07.2018
• Titel Quelle: Enthalten in: Biointerphases
• Ort Quelle: Melville, NY : AIP, 2006
• Jahr Quelle: 2012
• Band/Heft Quelle: 7(2012,1) Artikel-Nummer 23, 11 Seiten
• ISSN Quelle: 1559-4106
• DOI: doi:10.1007/s13758-012-0023-0
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577828607

Abstract

Substrates coated with specific bioactive ligands are important for tissue engineering, enabling the local presentation of extracellular stimulants at controlled positions and densities. In this study, we examined the cross-talk between integrin and epidermal growth factor (EGF) receptors following their interaction with surface-immobilized Arg-Gly-Asp (RGD) and EGF ligands, respectively. Surfaces of glass coverslips, modified with biotinylated silane-polyethylene glycol, were functionalized by either biotinylated RGD or EGF (or both) via the biotin-NeutrAvidin interaction. Fluorescent labeling of the adhering A431 epidermoid carcinoma cells for zyxin or actin indicated that EGF had a dual effect on focal adhesions (FA) and stress fibers: at low concentrations (0.1; 1 ng/ml), it stimulated their growth; whereas at higher concentrations, on surfaces with low to intermediate RGD densities, it induced their disassembly, leading to cell detachment. The EGF- dependent dissociation of FAs was, however, attenuated on higher RGD density surfaces. Simultaneous stimulation by both immobilized RGD and EGF suggest a strong synergy between integrin and EGFR signaling, in FA induction and cell spreading. A critical threshold level of EGF was required to induce significant variation in cell adhesion; beyond this critical density, the immobilized molecule had a considerably stronger effect on cell adhesion than did soluble EGF. The mechanisms underlying this synergy between the adhesion ligand and EGF are discussed.