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In this section, we will investigate the possibility of using wireframe DNA origami as force‐producing molecular machines in biological contests.

Mechanosensitive cellular receptors allow cells to sense the mechanical properties of their environment, especially those arising from the interaction between cells and the extracellular matrix [63]. In these receptors, chemical (receptor‐ligand interactions) and mechanical activations are combined to activate downstream signal processes [64]. One well‐studied example of mechanosensitive cellular receptors is the Notch receptor, for which it has proven that the binding of the ligand is not sufficient for the activation of the receptor and a mechanical force is also necessary [65]. Recent studies found that the force necessary for the activation of the Notch receptor seems to be higher than 4 pN and lower than 12 pN [65, 66].

The mechanical properties of single‐stranded and double‐stranded DNA (ssDNA and dsDNA) are considerably different [67]. While dsDNA can be considered rather stiff over a range of tens of nanometers, ssDNA behaves like a flexible and coiled polymer on the scale of a few nanometers. These mechanical properties have been used to create prestressed, tensegrity DNA nanostructures [68]. Tensegrity (or tensional integrity) is a property of a structure relying on a balance between components that are either in pure compression or in pure tension. In their work, Liedl et al. demonstrated that ssDNA can act as an entropic spring to prestress DNA bundles into stable structures. They used the force generated by the prestressing ssDNA to bend the DNA bundles or enzymatically actuate the entire structure.

We propose here a similar actuation mechanism applied to wireframe DNA origami nanostructures, which might be used for activation of mechanosensitive receptors in cells. We think that wireframe nanostructures could be more suitable for this task because of the highest resistance to degradation showed by these in biological media [47, 55]. In addition, the ssDNA springs segments are more easily implemented in the design of wireframe nanostructures, where the edges are often composed of single or double helices.