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In recent years, DNA origami has proved to be a valid and powerful technique for construction of structures on the nanoscale, ranging from small 2D sheets to large 3D structures [1–3]. The most common design paradigm is based on tightly packed helices and the use of the design software caDNAno [4]. Using this software, the target shape is “sculpted” from lattices (usually honeycomb or square) of densely packed helices, abstracted as cylinders [5, 6]. Twisted and curved structures have also been designed by introducing asymmetric insertions or deletions of base pairs in the helices [7, 8]. These structures have found application in a substantial number of fields: examples can be found in super‐resolution microscopy [9], biomedical research [10, 11], photonics [12, 13], and nanofabrication [14–16]. These applications have been helped by the presence of the GUI caDNAno and the existence of diverse computational framework to simulate the final design, such as the finite‐element‐based CanDo [17], the coarse‐grained simulation software oxDNA [18–20] or the more recent multi‐resolution simulation framework mrDNA [21].

Nonetheless, this DNA origami design has some limitations and drawbacks. The first limitation is the constraint to lattices of closely packed helices only, which makes it difficult (although not impossible) to create open, material‐efficient or porous nanoscale structures, especially for nonexperts. Another drawback is the low stability of these lattice‐based structures in low‐salt buffers: because of the repulsion between the helices, high concentrations of cations are required to keep the structures from unfolding. Although new methods have largely addressed this issue [22–24], the low stability can be a serious issue for the use of DNA origami in the biomedical field.

An alternative to these block‐like structures are polygonal wireframe designs, commonly used in 3D computer graphics design and modern architecture (where they are also called space frames). These structures are usually based on a mesh, i.e. a set of shape‐defining vertices, edges, and faces. In architecture, these designs are usually made rigid through tessellation, which provides a high strength‐to‐weight ratio. In addition, they are more space‐efficient, meaning that a bigger area can be covered with less material [25].

Because of these advantages, the attempts on constructing wireframe DNA origami have increased rapidly. Here, we review how the wireframe principles have been applied in DNA origami and subsequently introduce new in silico data showing how these kinds of structures can be valuable tools for molecular force generation.

Mechanobiology examines how biological systems respond to mechanical stresses [26–29]. Mechanical forces are ubiquitous in vivo, and it has been demonstrated how they regulate a wide variety of biological processes [26], such as changes in focal adhesion dynamics [30, 31], activation of mechanosensitive channel at the membrane [32], or nuclear localization of mechanosensitive transcriptional regulators [33]. DNA origami nanostructures have been used with success in different studies to measure the force produced or required by different biological processes [34–37]. In addition, DNA origami has also been used to guide the cellular behavior, interfacing with cellular receptors [11, 38]. We think that DNA origami nanostructures can be a valuable tool to study mechanobiology, and in the last section, we propose a DNA origami nanostructure design that could be used to apply mechanical force on cellular receptors.