A bioinspired design principle for DNA nanomotors: Mechanics-mediated symmetry breaking and experimental demonstration Juan Cheng a , Sarangapani Sreelatha a , Iong Ying Loh a,b , Meihan Liu a , Zhisong Wang a,b,⇑ a Department of Physics, National University of Singapore, Singapore 117542, Singapore b NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117542, Singapore article info Article history: Available online 3 March 2014 Keywords: Molecular motor DNA nanotechnology Azobenzene abstract DNA nanotechnology is a powerful tool to fabricate nanoscale motors, but the DNA nanomotors to date are largely limited to the simplistic burn-the-bridge design principle that prevents re-use of a fabricated motor-track system and is unseen in biological nanomotors. Here we propose and experimentally dem- onstrate a scheme to implement a conceptually new design principle by which a symmetric bipedal nanomotor autonomously gains a direction not by damaging the traversed track but by fine-tuning the motor’s size. Ó 2014 Elsevier Inc. All rights reserved. 1. Introduction A direction of DNA nanotechnology is to develop designed DNA structures into functional devices. A target is nanoscale motors [1] capable of continual directional motion beyond switch-like devices. A central problem to solve in designing and fabricating a nanomotor is how to rectify a net directional motion for a motor as a whole given the fact that its molecular components are each alone incapable of any directional drift. Artificial nanomotors [2–18] to date mostly use burn-the-bridge methods [3,7,8,10,13–16] to gain motor-level directionality. Namely, the traversed track (or an equivalent struc- tural component) is chemically damaged in the wake of the moving motor to prevent its backward motion. The burn-the-bridge meth- ods render the track not re-usable and are not seen in biological nanomotors [19,20] that inspired the artificial ones. Other methods to render a motor a net direction are also reported. An ordered administration of multiple strands is shown [4,5] to drive a motor with chemically different pedal components. A physically more sophisticated method [9,12] is also reported that enables a symmet- ric bipedal nanomotor to autonomously consume a fuel preferen- tially at the rear leg and thereby to gain a direction. Interestingly, a latest theory [21] suggests the possibility of using mechanical effects to improve this method, e.g., to add a forward bias for leg placement. A conceptually new design principle was proposed [22] and experimentally developed [17,18] recently for motor-level direction rectification in a non-destructive way [17] and with an integration [18] of preferential rear leg dissociation and biased forward leg placement. This design principle, termed mechanics- mediated symmetry breaking [22], was extracted from biomotos [19,20,23,24] and generalized for implementation in artificial motors. By this design principle, the motors may be symmetric bi- peds that can be fabricated by dimerizing identical synthetic pedal components, and the tracks may be a periodic array of merely two species of footholds (i.e., the minimum number of different foot- hold species required for an asymmetric track). But such a sym- metric bipedal motor may gain a direction on such a minimally heterogeneous track by simply fine-tuning the size of the motor, under the condition that a track-bound pedal component induces a local alignment along the track. Then the motor may be driven into continual directional run under random execution of a single operation designed to break the foot-track binding associated with the alignment. In this paper, we outline and experimentally demonstrate a gen- eral scheme to implement the design principle based on local migra- tion, which is applicable not only to DNA motors as shown in this study, but potentially also to nanomotors constructed from peptides and synthetic polymers. 2. Materials and methods 2.1. Strands and sequences for the DNA motor-track system The nucleotide sequences for the DNA strands were first selected using the NuPack server (www.nupack.org). Secondary structures http://dx.doi.org/10.1016/j.ymeth.2014.02.029 1046-2023/Ó 2014 Elsevier Inc. All rights reserved. ⇑ Corresponding author at: Department of Physics, National University of Singapore, Singapore 117542, Singapore. E-mail address: phywangz@nus.edu.sg (Z. Wang). Methods 67 (2014) 227–233 Contents lists available at ScienceDirect Methods journal homepage: www.elsevier.com/locate/ymeth