Recent work has refocused on the traction forces that cells impart on the substrate

on which they adhere. By using low moduli micropatterned substrates, [87 and

unpatterned "wrinkling" substrates,196-100] studies have begun to quantify these forces for

specific systems. Harris et al. first introduced the study of cell locomotion and adhesion

with wrinkling substrates by growing a wide variety of cells on a thin, heat-crosslinked

film of silicone floating on a silicone fluid. As the cells grow, they pull the film

underneath in circumferential folds that are smoothed out when the cells are trypsinized

from the surface.[96] Pelham and Wang were able to grow fibroblasts on polyacrylamide

substrates with very low moduli but varying 12-fold. They found that fibroblasts spread

less and had increased motility and lamellipodial activity on more flexible substrates,

while more rigid substrates promoted stable elongated focal adhesions.[98] Surprisingly,

this is one of the few studies examining the effect of different moduli of similar materials

on cell growth, and none to date have been reported that compare the effect of modulus to

the contact guidance phenomenon.

 Balaban et al. used fibroblasts stained to expose the focal adhesions of fibroblasts

grown on low modulus (E' 15 kPa) silicone elastomers with either fluorescent patterns

embedded into the surface, or features similar to pits and pillars as part of the surface.

The textures on their surfaces were 0.3 [im deep, because they wanted to minimize the

contact guidance phenomenon. With features deeper than that, polarization and directed

growth occurred along the features. In relating the displacement of the features with the

locations of the focal adhesions, they were able to extract force measurements exerted by

the focal points.[87]