Properly functioning cell-instructive biointerfaces are critical for healthy integration of biomedical devices in the body and serve as decisive tools for the advancement of our understanding of fundamental cell biological phenomena. Covalent chemistries to fabricate cell-instructive biointerfaces typically result in a static presentation of predefined cell-instructive cues. Chemically defined, but dynamic cell-instructive biointerfaces introduce spatiotemporal control over cell-instructive cues and present another type of biointerfaces, which promises a more biomimetic way to guide cell behavior. Therefore, strategies that offer control over the lateral sorting of ligands, the availability and molecular structure of bioactive ligands and strategies that offer the ability to induce physical, chemical and mechanical changes in-situ are implemented in cell-instructive interfaces. We use the novel biointerfaces to deepen our understanding of molecular and cellular biological processes investigating cell type specific responses and we undertake the translational steps towards targeted in-vivo applications.