A Chiral 2D Sheet for Enhancing GLUT1 Function Through the Interplay of Architecture and Recognition

ABSTRACT Controlling cellular function from the extracellular space requires synthetic materials capable of specific and sustained interactions at the cell membrane. This typically demands a synergy between the material's overall architecture and its molecular‐level recognition motifs. Here, we demonstrate this synergistic principle using a glucose‐based amphiphile that can be assembled into two distinct architectures. While the amphiphile alone forms 0D nanoparticles that are readily internalized by cells, its co‐assembly with a molecular trigger yields 2D nanosheets that remain on the cell exterior. This 2D morphology provides the necessary platform for sustained cell‐surface interaction, while the chirality of the glucose units acts as the specific recognition key. We show that only the 2D sheets presenting d ‐glucose effectively upregulate the membrane protein GLUT1 and trigger a downstream antioxidant response. This function is absent for the internalized 0D particles and the enantiomeric ( l )‐sheets, providing a clear demonstration of the powerful and essential synergy between supramolecular morphology and molecular chirality for the precise control of cellular behavior.