Surface density profile of bioadhesive ligands greatly influences spreading and migration of cells on substrates. A ID peeling model is developed to predict the equilibrium adhesion strength and peeling tension of a cell membrane, adhered on a substrate with linearly increasing density of ligands. Cell membrane is modeled as a linear elastic shell subjected to a tensile force applied at the free extremity and adhesive traction due to specific receptor-ligand interactions with the substrate. Membrane peeling tension increased with gradient slope and reached an asymptotic limit independent of gradient slope but proportional to receptor-ligand interaction energy. Peeling tension from substrates with negative gradient slope, at the rear edge of adhesion zone, was considerably lower than the tension from substrates with positive gradient slope at the leading edge, indicating that detachment is more likely to be initiated at the rear edge. This prediction leads to a possible mechanism for experimentally observed haptotactic locomotion of motile cells toward the direction of higher ligand density. (C) 2009 American Institute of Chemical Engineers AIChE J, 55: 2966-2972, 2009