Modified silicon surfaces for controlled cell interactions

Download files
Access & Terms of Use
open access
Copyright: Le Saux, Guillaume Marcel Louis
Altmetric
Abstract
Vital cellular processes such as adhesion, migration, differentiation and apoptosis are closely dependent on the interaction of the integrin receptors present on the outer membrane of cells with proteins that compose the extracellular matrix (ECM). The peptide sequence Arg–Gly–Asp (RGD), present in many of the extracellular proteins, has been found to play a dominating role in cell adhesion, where the integrin–RGD ligand system acts as an anchoring point to the substratum. Importantly, clusters of RGD–engaged integrin, called focal adhesions, act as plugs that induce multiple intracellular signaling pathways which regulate cell behavior. The ECM displays diverse chemical and topographical environments. Understanding how RGD ligand density, topography and ligand clustering modulate cell behavior is therefore crucial for research in cancer as well as for biomaterials or biosensors. The present work describes how modified silicon surfaces can be used to mimic the chemical and topographical aspects of the ECM. Investigating specific cell–surface interactions requires 1) RGD ligands with adjustable surface densities presented atop a bio–inert background, 2) control over substrate topography while ensuring the integrity of surface chemistry, 3) explicit distribution of RGD ligands in spots of tuneable sizes and numbers. Based on the hydrosilylation of 1-alkene moieties on silicon, biocompatible multilayer systems that meet these criteria are constructed and characterized. The spacing of RGD ligands of 50–100 nm is shown to influence the phenotype of endothelial cells and thus demonstrates the vital role of the spatial arrangement of ECM motifs in angiogenesis. Furthermore, even though cells display the expected behavior towards surface roughness, these remain sensitive to variations in RGD ligand spacing, suggesting that the spatial arrangement of the ECM motifs and substrate topography are not codependent. Finally, it is revealed that cells are less sensitive to RGD ligand spacing when integrins have the possibility to form localized clusters and hence, that integrin clustering balances the effects of ligand spacing on cell response.
Persistent link to this record
Link to Publisher Version
Link to Open Access Version
Additional Link
Author(s)
Le Saux, Guillaume Marcel Louis
Supervisor(s)
Gooding, J. Justin
Gaus, Katharina
Creator(s)
Editor(s)
Translator(s)
Curator(s)
Designer(s)
Arranger(s)
Composer(s)
Recordist(s)
Conference Proceedings Editor(s)
Other Contributor(s)
Corporate/Industry Contributor(s)
Publication Year
2010
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
Files
download whole.pdf 2.65 MB Adobe Portable Document Format
Related dataset(s)