Effect of Ligand Density Gradient on the Adhesion Kinetics of Biological Membranes
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1063-OO01-10
Effect of Ligand Density Gradient on the Adhesion Kinetics of Biological Membranes Alireza Sarvestani, and Esmaiel Jabbari Department of Chemical Engineering, University of South Carolina, 301 South Main St., Columbia, SC, 29208 ABSTRACT An analytical model is developed for the effect of surface gradient in ligand density on the adhesion kinetics of a curved elastic membrane with mobile receptors. The displacement and speed of spreading at the edge of the adhesion zone as well as the density profile of receptors along the membrane are predicted as a function of time. According to results, in the diffusioncontrolled regime, the front edge displacement of adhesion zone and the rate of membrane spreading decreased with increasing ligand density in a certain direction. Furthermore, the displacement of the edge of the adhesion zone did not scale with the square root of time, as observed on substrates with uniform ligand density. INTRODUCTION Cell spreading on substrates is a dynamic process involving non-covalent association between membrane receptors on the cell surface and complementary ligands on the substrate. The following limiting regimes can be defined for the displacement kinetics at the edge of the adhesion zone [1]: (1) reaction-controlled regime, in which the formation and breaking of cellsubstrate contacts are controlled by the rate of reversible reaction between the ligands ( L ) and receptors ( R ) L + R ↔ LR ; (1) (2) diffusion-controlled regime, in which the mobile receptors are recruited from the regions on the membrane far away from the adhesion zone [2-4]. At low receptor concentrations, the characteristic time for receptor diffusion is longer than that for the ligand-receptor reaction, and hence cell spreading is mediated by diffusion of mobile receptors. At high receptor concentrations, the rate of spreading of the adhesion zone is controlled by the rate of ligandreceptor association. Cell migration experiments demonstrate that cell-substrate interactions increase with ligand density up to a critical value, above which cell density and speed of migration reach either a plateau value or decrease [5-8]. Other experimental results with fibroblasts on substrates coated with gradient density of arginine-glycine-aspartate (RGD) tripeptide ligands [9] show higher cell adhesion in the direction of increasing RGD density. However, saturation effect is observed above a certain density of adhesive ligands where increasing the RGD density no longer improves cell adhesion. In the present work, we propose a model to examine the effect of gradient in surface ligand density on the kinetics of membrane adhesion. In the reaction-controlled regime (see Eq. (1)), increasing the ligand density should promote the membrane-substrate binding [1]. The situation, however, is quite different when adhesion is diffusion-controlled (i.e., at high ligand concentration). Therefore, we focus on the case of cell spreading and adhesion on gradient substrates in the diffusion-controlled regime. The model predicts that in
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