Here we address research directions and trends developed following novel concepts in 2D/3D self-assembled polymer structures established in the department led by Helmuth Möhwald. These functional structures made of hybrids of polymer multilayers, lipids, and nanoparticles stimulated research in the design of the cellular microenvironment. The composition of the extracellular matrix (ECM) and dynamics of biofactor presentation in the ECM can be recapitulated by the hybrids. Proteins serve as models for protein-based biofactors such as growth factors, cytokines, hormones, and so forth. A fundamental understanding of complex intermolecular interactions and approaches developed for the externally IR-light-triggered release offers a powerful tool for controlling the biofactor presentation. Pure protein beads made via a mild templating on vaterite CaCO3 crystals can mimic cellular organelles in terms of the compartmentalization of active proteins. We believe that an integration of the approaches developed and described here offers a strong tool for engineering and mimicking both extra- and intracellular microenvironments.