Experimental evidence for shifting stiffness optima. (A) Cell migration data for neutrophils (10), NIH/3T3 fibroblasts (2), U87 glioma cells (4), and smooth muscle cells (11) show varying dependence on stiffness. For U87 glioma cells and smooth muscle cells, experimentally measured migration increases with substrate stiffness. For NIH/3T3 fibroblasts it decreases with stiffness, and for neutrophils it increases and then decreases with stiffness. These results suggest a biphasic dependence of cell migration on substrate stiffness; therefore, Gaussian curves were fit to the data to show potential stiffness optima. (B) Traction force data for embryonic chick forebrain neurons (15), T24 bladder cancer cells (7), and bovine aortic endothelial cells (12) also show varying dependence on substrate stiffness. For embryonic chick forebrain neurons, traction force decreases with stiffness, whereas for T24 bladder cancer cells and bovine aortic endothelial cells it increases with stiffness. This also suggests a biphasic response, and Gaussian curves were fit to the data to show potential stiffness optima. For both A and B, data were normalized to the maximum value for the particular cell type, therefore all data can be shown easily on one plot. Dashed lines indicate extrapolation of the Gaussian curves beyond the given data.