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Abstract
Migration of mammalian blood and tissue cells over adhesive surfaces is apparently
mediated by specific reversible reactions between cell membrane adhesion receptors
and complementary ligands attached to the substratum. Although in a number of systems
these receptors and ligand molecules have been isolated and identified, a theory capable
of predicting the effects of their properties on cell migration behavior currently
does not exist. We present a simple mathematical model for elucidating the dependence
of cell speed on adhesion-receptor/ligand binding and cell mechanical properties.
Our model can be applied to propose answers to questions such as: does an optimal
adhesiveness exist for cell movement? How might changes in receptor and ligand density
and/or affinity affect the rate of migration? Can cell rheological properties influence
movement speed? This model incorporates cytoskeletal force generation, cell polarization,
and dynamic adhesion as requirements for persistent cell movement. A critical feature
is the proposed existence of an asymmetry in some cell adhesion-receptor property,
correlated with cell polarity. We consider two major alternative mechanisms underlying
this asymmetry: (a) a spatial distribution of adhesion-receptor number due to polarized
endocytic trafficking and (b) a spatial variation in adhesion-receptor/ligand bond
strength. Applying a viscoelastic-solid model for cell mechanics allows us to represent
one-dimensional locomotion with a system of differential equations describing cell
deformation and displacement along with adhesion-receptor dynamics. In this paper,
we solve these equations under the simplifying assumption that receptor dynamics are
at a quasi-steady state relative to cell locomotion. Thus, our results are strictly
valid for sufficiently slow cell movement, as typically observed for tissue cells
such as fibroblasts. Numerical examples relevant to experimental systems are provided.
Our results predict how cell speed might vary with intracellular contractile force,
cell rheology, receptor/ligand kinetics, and receptor/ligand number densities. A biphasic
dependence is shown to be possible with respect to some of the system parameters,
with position of the maxima essentially governed by a balance between transmitted
contractile force and adhesiveness. We demonstrate that predictions for the two alternative
asymmetry mechanisms can be distinguished and could be experimentally tested using
cell populations possessing different adhesion-receptor numbers.