Many model systems and measurement tools have been engineered for observing and quantifying the effect of mechanics on cellular response. These have contributed greatly to our current knowledge of the molecular events by which mechanical cues affect cell biology. Cell responses to the mechanical properties of type 1 collagen gels are discussed, followed by a description of a model system of very thin, mechanically tunable collagen films that evoke similar responses from cells as do gel systems, but have additional advantages. Cell responses to thin films of collagen suggest that at least some of the mechanical cues that cells can respond to in their environment occur at the sub-micron scale. Mechanical properties of thin films of collagen can be tuned without altering integrin engagement, and in some cases without altering topology, making them useful in addressing questions regarding the roles of specific integrins in transducing or mitigating responses to mechanical cues. The temporal response of cells to differences in ECM may provide insight into mechanisms of signal transduction.