MAXIMAL MIGRATION OF HUMAN SMOOTH-MUSCLE CELLS ON FIBRONECTIN AND TYPE-IV COLLAGEN OCCURS AT AN INTERMEDIATE ATTACHMENT STRENGTH

Although a biphasic dependence of cell migration speed on cell-substra tum adhesiveness has been predicted theoretically, experimental data d irectly demonstrating a relationship between these two phenomena have been lacking. To determine whether an optimal strength of cell-substra tum adhesive interactions exists for cell migration, we measured quant itatively both the initial attachment strength and migration speed of human smooth muscle cells (HSMCs) on a range of surface concentrations of fibronectin (Fn) and type IV collagen (CnIV). Initial attachment s trength was measured in order to characterize short time-scale cell-su bstratum interactions, which may be representative of dynamic interact ions involved in cell migration. The critical fluid shear stress for c ell detachment, determined in a radial-flow detachment assay, increase d linearly with the surface concentrations of adsorbed Fn and CnIV. Th e detachment stress required for cells on Fn, 3.6 +/- 0.2 X 10(-3) mud ynes/absorbed molecule, was much greater than that on CnIV, 5.0 +/- 1. 4 X 10(-5) mudynes/absorbed molecule. Time-lapse videomicroscopy of in dividual cell movement paths showed that the migration behavior of HSM Cs on these substrates varied with the absorbed concentration of each matrix protein, exhibiting biphasic dependence. Cell speed reached a m aximum at intermediate concentrations of both proteins, with optimal c oncentrations for migration at 1 X 10(3) molecules/mum2 and 1 X 10(4) molecules/mum2 on Fn and CnIV, respectively. These optimal protein con centrations represent optimal initial attachment strengths correspondi ng to detachment shear stresses of 3.8 mudyne/mum2 on Fn and 1.5 mudyn e/mum2 on CnIV. Thus, while the optimal absorbed protein concentration s for migration on Fn and CnIV differed by an order of magnitude, the optimal initial attachment strengths for migration on these two protei ns were very similar. Further, the same minimum strength of initial at tachment, corresponding to a detachment shear stress of approximately 1 mudyne/mum2, was required for movement on either protein. These resu lts suggest that initial cell-substratum attachment strength is a cent ral variable governing cell migration speed, able to correlate observa tions of motility on substrata differing in adhesiveness. They also de monstrate that migration speed depends in biphasic manner on attachmen t strength, with maximal migration at an intermediate level of cell-su bstratum adhesiveness.