Stochastic model of biased cell migration based on binding fluctuations of adhesion receptors

Recently much research has focused on how the composition of extracellular matrix and the spatial distribution of its components influence the extent and direction of cell locomotion via receptor-specific adhesion. There is evidence that gradients of adhesion molecules influence the direction of cell migration, a phenomenon known as haptotaxis. Whether these responses are the result of an intracellular signalling process or simply a passive adhesion differential is presently unknown. A stochastic model of an idealized motile cell undergoing adhesion receptor-mediated movement is developed to ascertain the consequences of statistical fluctuations in binding of adhesion receptors. It is used to address how the magnitude of adhesion may affect cell movement parameters such as mean cell speed and persistence time. Also considered is how a gradient of adhesion can yield cell directional orientation and direction-dependent speed (orthotaxis), and under what conditions haptotaxis is predicted from passive adhesion differential only. Model predictions of biased movement are given explicitly in terms of parameters which determine the quantity and spatial distribution of cell surface adhesion receptors as well as in terms of the adhesion gradient. Predictions are compared to data for meclanoma cells migrating on surfaces covered with Arg-Gly-Asp (RGD)-containing peptide.