The mechanics of cellular processes are determined by the cytoskeleton, a biopolymer network which spans the cell and provides it with mechanical strength. Cells have the capability to autonomously adapt structure and mechanical properties of their cytoskeletal network to changes in physical properties of the surrounding tissue, for which mechanosensing processes play an important role, allowing cells to sense those changes through their focal adhesions. The active adaptability of cellular mechanics has in part its origin in cytoskeletal protein motors (myosin II). An important part of the effort to elucidate how motor activity controls cell mechanics has focused on the rheology of in vitro actin cross-linked networks.The key to understand the mechanical adaptability of the actin cytoskeleton appears to be the poorly understood interplay between the activity of molecular motors and the mechanical properties, dictated to a large extent by cross-linkers. This proposal aims to fill that gap by adopting a unique experimental approach: a model system based on actin filaments grafted with DNA strands that form cross-links by specific base-pairing. The use of DNA strands as cross-linkers will give me unprecedented control over both strength and compliance of cross-links between actin filaments. A bottom-up approach will allow me to study, combining microscopy and rheology techniques, how cytoskeletal self-organization and mechanical properties depend on cross-linker compliance and motor activity, and to explore the formation of cell-substrate adhesions using a biomimetic model of a mechanosensing cell.This approach will provide for the first time a molecular understanding of cytoskeletal network mechanics, and allow for the development of quantitative theoretical models. My proposal will lay the foundation for new cell-inspired biomaterials of mechanical properties tailored on the molecular scale, with potential applications in tissue engineering and materials science.