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.
Kim et al. (Mon,) studied this question.