Engineered environments for cell fate decisions - The function of a cell is, in part, regulated by its surrounding tissue microenvironment. The chemical composition and mechanical properties of this environment provide essential cues that direct stem cells toward specific fates. In this talk, I will describe our efforts to design hydrogels with independently tunable properties for stem cell and organotypic cultures. Using biomaterials design approaches, we aim to uncover the underlying biological mechanisms that drive the onset and progression of pancreatic cancer, fatty liver disease, and aging of the hematopoietic system. I will highlight our recent work using induced pluripotent stem cell-derived hematopoietic cells to identify environmental features that support aging of the blood and immune systems. Through studies of both biological tissues and engineered gels, we have identified regimes of nonlinear mechanical properties that influence stem cell fate. At low stresses and strains, material properties such as stiffness and stress relaxation are typically independent of the applied force. However, as cells exert more force, they encounter stress-dependent behaviors, such as strain stiffening. To better inform the design of biomaterials, we developed a mechanical model that characterizes material behavior across both short and long timescales and under both low and high stress. This model has enabled us to characterize biological tissues and gels for the rational design of hydrogels that recapitulate the complex properties of in vivo tissues. I will finish with a discussion of our bone marrow-mimetic platform, using a thermoreversible synthetic polypeptide, to interrogate external factors that influence the aging of the blood and immune systems.