A dynamical model for receptor-mediated cell adhesion to surfaces in viscous shear flow.
We present a dynamical model for receptor-mediated cell adhesion to surfaces in viscous shear flow when the surfaces are coated with ligand molecules complementary to receptors in the cell membrane. This model considers the contact area between the cell and the surface to be a small, homogeneous region that mediates the initial attachment of the cell to the surface. Using a phase plane analysis for a system of nonlinear ordinary differential equations that govern the changes in free receptor density and bond density within the contact area with time, we can predict the conditions for which adhesion between the cell and the surface will take place. Whether adhesion occurs depends on values of dimensionless quantities that characterize the interaction of the cell and its receptors with the surface and its ligand, such as the bond formation rate, the receptor-ligand affinity, the fluid mechanical force, the receptor mobility, and the contact area. A key result is that there are two regimes in which different chemical and physical forces dominate: a rate-controlled high affinity regime and an affinity-controlled low affinity regime. Many experimental observations, including the effects of temperature and receptor mobility on adhesiveness, can be explained by understanding which of these regimes is appropriate. We also provide simple approximate analytical solutions, relating adhesiveness to cell and surface properties as well as fluid forces, which allow convenient testing of model predictions by experiment.
Hammer
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School of Chemical Engineering, Cornell University, Ithaca, NY 14853.
Lauffenburger
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D000818:Animals; D002448:Cell Adhesion; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology*
D011956:Receptors, Cell Surface