Biomimetic Dynamics of Nanoscale Groove and Ridge Topography for Stem Cell Regulation

Abstract Native extracellular matrix exhibits multiscale groove and ridge structures that continuously change, such as collagen fibril‐based nanogrooves in bone tissue, and regulate cellular responses. However, dynamic switching between groove and ridge nanostructures at the molecular level has not been demonstrated. Herein, materials capable of dynamic groove‐ridge switching at tens‐of‐nanometers scale are developed by flexibly conjugating RGD‐magnetically activatable nanoridges (MANs) to non‐magnetic nanogrooves with independently tuned widths comparable to the sizes of integrin‐presenting filopodia by modulating hydrophobicity in bicontinuous microemulsion, allowing for cyclic modulation of RGD accessibility and cellular adhesion. Nanogrooves with medium width restrict RGD accessibility in the “groove” state in which the RGD‐MANs are buried, which is reversed by magnetically raising them to protrude and form the “ridge” state that fully exposes the RGDs. This reversibly stimulates integrin recruitment, focal adhesion complex assembly, mechanotransduction, and differentiation of stem cells in vivo. This is the first demonstration of molecular‐level groove and ridge nanostructures that exhibit unprecedented switchability between groove and ridge nanostructures. Versatile tuning of the width, height, pitch, and shape of intricate nanogroove structures with remote manipulability can enlighten the understanding of molecular‐scale cell–ligand interactions for stem cell engineering‐based treatment of aging, injuries, and stress‐related diseases.