pH-Driven Actuation of DNA Origami via Parallel I-Motif Sequences in Solution and on Surfaces

Abstract

As bottom up DNA nanofabrication creates increasingly complex and dynamic mechanisms, the implementation of actuators within the DNA nanotechnology toolkit has grown increasingly important. One such actuator, the I-motif, is fairly simple in that it consists solely of standard DNA sequences and does not require any modification chemistry or special purification beyond that typical for DNA oligomer synthesis. This study presents a new implementation of parallel I-motif actuators, emphasizing their future potential as drivers of complex internal motion between substructures. Here we characterize internal motion between DNA origami substructures via AFM and image analysis. Such parallel I-motif design and quantification of actuation provide a useful step toward more complex and effective molecular machines.

Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics, and Therapeutic Applications

“…The flexibility of this system, and the fact that this work proved the functionality of the tetrahedral sensors in vivo, allow a wide range of smart biosensing and detection at the cellular level . Recently, LaBean and co‐workers synthesized DNA origami that was able to actuate spatially through the incorporation of i‐motif sequences (Figure B). The authors mentioned that the length of the actuation can be designed through the length of the i‐motif sequence .…”

“…DNA sequences that are rich in cytosine can form two intercalated parallel duplexes under low pH through the hemiprotonation of a cytosine–cytosine pair . This structure has a height proportional to the length of the ssDNA sequence . Consequently, this structural formation change can be incorporated into DNA nanodevices for usage in biomapping and therapeutic delivery due to the acidification of late stage endosomes .…”

“…Recently, LaBean and co‐workers synthesized DNA origami that was able to actuate spatially through the incorporation of i‐motif sequences (Figure B). The authors mentioned that the length of the actuation can be designed through the length of the i‐motif sequence . Thus, the incorporation of pH‐responsive DNA i‐motifs have many potential benefits to help understand and map cellular pH on a deeper level.…”

“…B) DNA origami actuated through the incorporation of the i‐motif sequence. Reproduced with permission . Copyright 2017, American Chemical Society.…”

“…This flexibility allows engineers to create hybrid nanostructures with both DNA and other materials, thus expanding the range of what DNA nanotechnology can be designed for. We can also include within these synthetic DNA structures, the potential for responsiveness to pH, light, or small molecule targets through incorporating DNA secondary structures such as DNA triplex structures or the intercalated cytosine motif, thus allowing us to create responsive nanostructures that can be classified as nanomachines. This responsiveness can also be derived from pre‐existing artificially selected for motifs called “aptamers” which selectively bind proteins and small molecules .…”