Mechanical Flexibility of DNA: A Quintessential Tool for DNA Nanotechnology

Abstract

The mechanical properties of DNA have enabled it to be a structural and sensory element in many nanotechnology applications. While specific base-pairing interactions and secondary structure formation have been the most widely utilized mechanism in designing DNA nanodevices and biosensors, the intrinsic mechanical rigidity and flexibility are often overlooked. In this article, we will discuss the biochemical and biophysical origin of double-stranded DNA rigidity and how environmental and intrinsic factors such as salt, temperature, sequence, and small molecules influence it. We will then take a critical look at three areas of applications of DNA bending rigidity. First, we will discuss how DNA’s bending rigidity has been utilized to create molecular springs that regulate the activities of biomolecules and cellular processes. Second, we will discuss how the nanomechanical response induced by DNA rigidity has been used to create conformational changes as sensors for molecular force, pH, metal ions, small molecules, and protein interactions. Lastly, we will discuss how DNA’s rigidity enabled its application in creating DNA-based nanostructures from DNA origami to nanomachines.

Mechanical Properties of DNA Hydrogels: Towards Highly Programmable Biomaterials

“…The nanoscale mechanical properties of DNA [122] are known to influence the bulk mechanical properties of the DNA hydrogels assembled [50,123]. Indeed, DNA has inherent nanoscale mechanical properties that depend on its structure and assembly [22,26]. It has an elastic modulus comprised between 0.3 and 1 GPa and a persistence length of 50 nm (~150 bp) in a duplex form [124].…”

“…The structural predictability provides the user with modeling capability and an exquisite control over the final assembly as well as great design flexibility [4,7,19,21]. In addition, the mechanical properties of DNA-based nanoarchitectures can be easily programmed by changing the type of DNA motifs used, the hybridization state, and their nanostructure design [22][23][24][25][26]. DNA materials are inherently biocompatible, self-assemble in solution, exhibit high structural stability, and their ease of modification makes them a great material to scaffold various organic and inorganic molecules with nanoscale precision to functionalize the nanoarchitectures [27][28][29][30].…”

Maximizing the Surface Sensitivity of LSPR Biosensors through Plasmon Coupling—Interparticle Gap Optimization for Dimers Using Computational Simulations

“…For nucleotide sensors (utilizing DNA and RNA molecules) a 5 nm layer thickness would equal a fully extended ds-DNA of 15 base pairs, which is an entirely realistic receptor–target length for plasmonic applications (for more information, see a survey of plasmonic nucleotide sensors in [ 12 ]). For the optimization of nucleotide sensors, one should consider that ss-DNA chains that compose the empty receptor layer usually do not extend to their full length; thus, the effective layer thickness increases upon hybridization (ds-DNA chains are less flexible [ 48 ]). The optimization of immunosensors should consider the sizes of the antibody (in the 10 nm range) and the analyte, which can vary significantly between applications.…”

Biophysical Approaches for Applying and Measuring Biological Forces

“…Recently, a visualization approach based on force‐sensitive molecules has drawn great attention in the investigation of mechanotransduction. [ 23 , 156 ] This technique is also named MFPs or molecular force sensors (MFSs). Through molecular‐based design, MFPs have overcome some of the limitations of traditional methods.…”