Solvent-Driven Competition of Chirality Transfer in Cyanostilbene-Based Dipeptide Amphiphiles and Correlating Supramolecular Helicity with Cell Proliferation

While chiral nanostructures have been fabricated across multiple hierarchical levels, the chirality transfer and amplification from molecular to supramolecular assemblies remain poorly understood, particularly in multichiral systems. Although helical nanofibers significantly influence cellular adhesion, the role of molecular chirality in regulating the cell behavior within these architectures is often overlooked. Herein, we report a dipeptide amphiphile system that deciphers the stereochemical regulation of supramolecular handedness propagation in multichiral environments, revealing synergistic solvent-polarity effects on the chirality hierarchy. Through molecular engineering, four stereoisomers of amphiphiles (abbreviated as CNGAC18)─featuring l/d-alanine (Ala) and l/d-glutamic acid (Glu) covalently linked to cyanostilbene chromophores and octadecyl chains─were synthesized, demonstrating solvent-responsive self-assembly into structurally defined architectures. Circular dichroism spectroscopy unveiled solvent-polarity-driven stereochemical dominance: Ala configuration dictates supramolecular chirality in polar media, whereas Glu stereocenters govern helical orientation in apolar environments. Homochiral LL/DD isomers form helical nanostructures with handedness conservation, while heterochiral LD/DL analogs exclusively yield achiral fibers. Notably, LL-derived left-handed nanohelices enhance cellular proliferation compared to right-handed DD counterparts, establishing a direct correlation between supramolecular helicity directionality and biointerface regulation. This work elucidates fundamental principles of multiscale chirality transfer and provides a stereochemical blueprint for the design of programmable biointerfacial materials.