Effect of Chirality on Cell Spreading and Differentiation: From Chiral Molecules to Chiral Self-Assembly

The influence of chirality on cell behavior is closely related with relevant biological events; however, many recent studies only focus on the apparent chiral influence of supramolecular nanofibers and ignore the respective effects of molecular chirality and supramolecular chirality in biological processes. Herein, the inherent molecular and supramolecular chiral effects on cell spreading and differentiation are studied. Left-handed nanofibers (referring to supramolecular chirality) assembled from L-amino acid derivatives can enhance cell spreading and proliferation compared to flat L-surfaces (referring to molecular chirality). However, compared to the D-surfaces (referring to molecular chirality), right-handed nanofibers (referring to supramolecular chirality) derived from D-amino acid suppress cell spreading and proliferation, overturning the conventional view that a fibrous morphology generally enhances cell adhesion. The results directly suggest that the amplification of chirality from chiral molecules to chiral assemblies significantly enhances the effect on regulated cell behavior by supramolecular helical handedness. Moreover, cell differentiation is found to be chirality dependent. It suggests that both the L-amino acid derivatives and the left-handed fibers facilitate osteogenic differentiation. This study provides useful insight into understanding the origin of chiral expression from the molecular to the macroscopic level in nature.