Non‐invasive Regulation of Cellular Morphology Using a Photoswitchable Mechanical DNA Polymer

Abstract

The 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.

Recent developments in DNA-based mechanical nanodevices

“…Very recently, Sethi et al reported a photo-switchable DNA nanospring using azobenzene-incorporated DNA strands. 88 After light irradiation, due to the cis – trans conformational change of azobenzene, the DNA hairpin structures can be reversibly folded/unfolded to induce the shrinking/relaxation of the DNA nanospring.…”

Biomimetic DNA Nanotechnology to Understand and Control Cellular Responses

“…Furthermore, our group recently developed a light-controlled dynamic DNA polymer which can extend and shrink reversibly by photoirradiation. [26] This photofunctionalized DNA polymer could behave as an ECM and reversibly changed the presentation of nanocues to the cells to control the morphology of mesenchymal stem cells. Significant changes in morphology, F-actin organization and vinculin distribution were observed among the cells.…”

“…A tool for mimicking ECM [26] in 3D cell culture (Figure 2a). [29] Thermo-reversible DNA hydrogels with high stretchability and integrated molecular toolbox of DNA tension probes were prepared and used as a fluorescent mechanochromic matrix (Figure 2b).…”

“…On similar lines, researchers created nanosprings by using principles of DNA origami, [25] coiling and uncoiling of their nanospring was controlled by the formation and dissolution of an i‐motif structure directed by pH changes. Furthermore, our group recently developed a light‐controlled dynamic DNA polymer which can extend and shrink reversibly by photoirradiation [26] . This photofunctionalized DNA polymer could behave as an ECM and reversibly changed the presentation of nanocues to the cells to control the morphology of mesenchymal stem cells.…”

In Vivo Activation of T-Cell Proliferation by Regulating Cell Surface Receptor Clustering Using a pH-Driven Interlocked DNA Nano-Spring

“…Recently, Sethi et al formulated a photoswitchable DNA nanostructure to dynamically regulate the spatial distance of RGD with photoirradiation, which can induce a significant morphology change in cells. 20 Yet, the previous methods are generally based on transitions between double-stranded DNA (dsDNA) and the DNA hairpin, whose mechanical strength is not stable enough for precise control of the spatial distribution between different ligands. On the other hand, DNA origami-based nanocalipers can present ligands at well-defined positions but lack stimuliresponsive reconfigurable properties.…”