Embryonic stem cells (ESCs) are increasingly being studied for use in regenerative medicine. However, current methods to differentiate ESCs into appropriate tissue-specific cell types do not result in a high enough yield to be therapeutically feasible. The proposed research examines the role of the physical micro-environment in ESC differentiation. It has been previously shown that substrate stiffness and surface micro-topography individually influence cellular differentiation. We hypothesize that the combination of substrate stiffness and surface micro-topography will enhance and accelerate ESC differentiation toward tissue-specific lineages.