Engineering Substrates for the Study of Cell Mechanical Interactions

This thesis describes the effect of geometries with controlled radius of curvature on cellular behavior, a novel approach to measure and map protrusive forces in cells and the application of fabrication techniques like wet etching and microcontact printing to answer fundamental biological problems. In order to isolate the effects of curvature from other factors, we have developed a technique to create features with nominally identical dimensions but varying radius of curvature. Using these substrates, we analyzed the effect of curvature on cell morphology. Cell area and aspect ratio were examined on various substrates, and immunostaining of focal adhesions, stress fibers and microtubules were used to show the effect of curvature on these cytoskeleton components. We show that feature curvature has an effect on both cell morphology and cytoskeleton organization. Using this technique, it may be possible to engineer precise geometries that can lead to better design of scaffolds and biomaterials for tissue engineering. The motivation behind measuring cellular forces was two fold, first to measure the protrusive forces locally and with spatial resolution and second to measure them at the