Cells sense and react to various extracellular matrix (ECM) cues including chemical and physical cues. Previous studies in our laboratory and others have used static substrates, where the elastic properties remain unchanged throughout the culture period, to examine the effects of mechanical stiffness on neuron and fibroblast behavior [1–4]. However, in vivo, the ECM is dynamic and alters due to pathological, developmental, and external factors [5]. To study the effects of dynamic ECM changes on cell behavior, we developed a DNA-crosslinked, polyacrylamide gel (DNA gel) that allows us to study how dynamic changes in ECM stiffness affect cell behavior [6, 7].