Reversible Tuning of Multiple Molecular Kinking for Stem Cell Regulation In Vivo

ABSTRACT In the native extracellular matrix, collagen fibrils regulate stem cell fate and tissue regeneration by modulating the number of serial kinks via intramolecular kinking and unkinking, which affects integrin ligation. However, biomimetic materials composed solely of multi‐kink‐bearing molecules for dynamic regulation of ligand exposure remain limited. In this study, we designed materials composed solely of liganded multiple kink‐bearing molecules with a tunable number of kink points (mono‐kink, tri‐kink, and penta‐kink molecules), including flexible linkers and densely packed via intermolecular interactions, are designed. Near‐infrared‐upconverted ultraviolet light and visible light induce multiple kinking and unkinking of liganded multiple kink‐bearing molecules conjugated to upconversion nanoparticle‐coated materials, inducing kinked and unkinked states, respectively. Tri‐kinking and unkinking mediate the effective regulation of ligand masking and exposure, respectively, by modulating intermolecular interactions, while mono‐kink and penta‐kink molecules continuously expose the ligands regardless of their kinking/unkinking state. Tri‐unkinking cyclically stimulates integrin ligation and focal adhesion‐mediated stem cell mechanotransduction and differentiation in vivo, which are inhibited by tri‐kinking. This study presents a newly developed reversibly switchable multi‐kink molecule‐conjugated surface for dynamic regulation of ligand exposure and stem cell responses, providing a useful modality for regulating cell–material interactions and stem cell fate in vivo.