Tissues are heterogeneous populations of cells that must self-organize to coordinate collective behaviors and arrive and collective decisions. Therefore, tissue structure plays a central role in orchestrating many multicellular processes. We are taking a bottom-up approach to study the relationship between tissue structure and function using the human mammary gland as a model system. We use DNA-based chemical adhesion molecules to build three-dimensional tissues with precisely defined sizes, shapes,and compositions using primary human cells and non-malignant cell lines as building blocks. We are using these tissues to understand how signaling heterogeneity among mammary epithelial cells can drive collective cell behaviors, how heterogeneous populations of cells can self-organize robustly, and how multiple cell types can coordinate their behaviors across the epithelial and stromal compartments to drive tissue remodeling.