# Mechanical Design of DNA Origami in the Classroom
## 1 Introduction  
The self-assembly process known as scaffolded DNA origami (DO) is a powerful approach to fabricating user-defined shapes with sizes on the order of tens to hundreds of nanometers and nanometer spatial resolution over structural features [1; 2; 3]. A major developing area of DO is to fabricate dynamic nanodevices that are able to perform programmed motions [4] or tasks such as signal transmission [5] or even computing [6]. These reconfigurable devices rely on actuated conformation changes, thermal fluctuations, and/or mechanical deformations of DNA structures. These nanomechanical designs provide a basis for devices with functions such as tunable force response and rapid reconfiguration and unique properties such as having a negative Poisson's ratio [7], all of which make DNA origami highly promising for a wide range of applications, such as biosensors [8], targeted or stimulus-responsive therapies [9], and nanomechanical measurement tools [10]. Given the wide range of applications, there is a need to broaden access to training on DO concepts and methods. Nanomechanical DNA origami structures also provide a unique platform to connect fundamental engineering concepts to molecular-scale design. Here, we present an experiment module that includes the folding and analysis of a DO device that can be folded into several distinct deformed configurations that can be examined by gel electrophoresis. We also present twomechanical models for describing the deformed shapes, thereby highlighting the connection to engineering concepts such as force response, material properties, and beam bending. The field of structural DNA nanotechnology was initiated decades ago with [PERSON]'s idea to build synthetic lattice structures from multi-arm DNA junctions [11]. The concept of making DNA nanodevices dynamic, or responsive to some external input, was also pioneered by [PERSON] and co-workers [12], and has become a major area of research and development [3]. Figure 1 illustrates several examples of nanomechanical DNA devices, highlighting their progression over multiple decades. The first demonstrations of reconfigurable DNA devices included systems wherein DNA strands or small structural motifs could be reconfigured via B-Z transition of DNA [12] or DNA strand displacement [13; 14; 15], and later, DNA structures that could be triggered into three states [16]. The development of scaffolded DNA origami [1] significantly advanced the geometric design space for DNA nanostructures, which also led to corresponding advances in complexity and functionality of nanomechanical DNA devices, including containers with controlled opening [17], nanoactators with reversibly reconfigurable structural elements [18], and dynamic structures exhibiting multiple stable states [19] or photoactivated shape changes [20]. Other recent examples have leveraged the ability to tune mechanical properties of components to create devices with various deformed states for polymorphic designs [21], or DNA origami, in which conversions between double- and single-stranded DNA cause shape changes [22]. These examples highlight the emergence of nanomechanical design in DNA nanotechnology; more extensive overviews of nanomechanical DNA devices are available in recent reviews [10; 23; 24]. Figure 1: Examples of DNA nanomechanical devices. (**A**): a DNA tweezer that is closed and opened through DNA binding and strand displacement interactions [13]. (**B**): A nanomechanical device where rotation of domains is induced by exchanging multiple DNA strands [14; 15]. (**C**): a DNA nanomechanical device with three robust states [16]. Copyright (2008) National Academy of Sciences. (**D**): A bistable DNA origami mechanism [19] (Reprinted (adapted) with permission from Direct Design of an Energy landscape with Bistable DNA Origami Mechanisms. [PERSON], et al., Nano Letters 2015 15(3), 1815–1821. DOI: 10.1021/nl5045633. Copyright (2015) American Chemical Society). (**E**): Polymorphic design of DNA origami through mechanical design of modular components [21].