Abstract
The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD) could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×102–6×1011 RGD/mm2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×105 RGD/mm2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×108 RGD/mm2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry.
Highlights
Cell adhesion to the extracellular matrix (ECM) plays a fundamental role in regulating cell differentiation, growth and survival [1,2,3] as well as cell morphology and phenotype [4]
Silicon (100) surfaces are exceedingly smooth with a root mean square (RMS) roughness of 1.260.2 nm (Fig. 2A)
The pyramids can be clearly seen with atomic force microscopy (AFM) as shown in Figure 2B–C and Figure S1
Summary
Cell adhesion to the extracellular matrix (ECM) plays a fundamental role in regulating cell differentiation, growth and survival [1,2,3] as well as cell morphology and phenotype [4]. Endothelial cell adhesion and migration requires that integrin receptors on the cell surface recognize and bind to ligands in the ECM [5]. One of those ligands is the arginineglycine-aspartic acid peptide sequence (RGD) which is present in fibronectin and other matrix proteins [6]. Because cancer growth often depends on the extent of neovascularization, understanding the fundamental properties of angiogenic transformation and the extracellular factors that contribute to this phenotype switch is important for therapeutic intervention and the design of implantable devices [7]
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