AbstractThe extracellular matrix (ECM) in which the cells reside provides a dynamic and reversible environment. Spatiotemporal cues are essential when cells are undergoing morphogenesis, repair and differentiation. Emulation of such an intricate system with reversible presentation of nanoscale cues can help us better understand cellular processes and can allow the precise manipulation of cell function in vitro. Herein, we formulated a photoswitchable DNA mechanical nanostructure containing azobenzene moieties and dynamically regulated the spatial distance between adhesion peptides using a photoswitchable DNA polymer with photoirradiation. We found that the DNA polymer reversibly forms two different structures, a relaxed linear and shrunken compact form, observed by AFM. Using the mechanical properties of this DNA polymer, UV and visible light irradiation induced a significant morphology change of the cells between a round shape and spindle shape, thus providing a tool to decipher the language of the ECM better.