Biomaterial scaffolds that are designed to incorporate dynamic, spatiotemporal information have the potential to interface with cells and tissues to direct behavior. Here we describe a bioinspired, programmable nanotechnology-based platform that harnesses cellular traction forces to activate growth factors, eliminating the need for exogenous triggers (e.g. light), spatially diffuse triggers (e.g. enzymes, pH changes) or passive activation (e.g. hydrolysis). We use flexible aptamer technology to create modular, synthetic mimics of the Large Latent Complex that restrains TGF-β1. This flexible nanotechnology-based approach is shown here to work with both platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF-165), integrate with glass coverslips, polyacrylamide gels, and collagen scaffolds, enable activation by various cells (e.g. primary human dermal fibroblasts, HMEC-1 endothelial cells) and unlock fundamentally new capabilities such as selective activation of growth factors by differing cell types (e.g. activation by smooth muscle cells but not fibroblasts) within clinically relevant collagen sponges.