Modular reconfiguration of DNA origami assemblies using tile displacement.

The power of natural evolution lies in the adaptability of biological organisms but is constrained by the time scale of genetics and reproduction. Engineeringartificial molecular machines should not only include adaptability as a core feature but also apply it within a larger design space and at a faster time scale. A lesson from engineering electromechanical robots is that modular robots can perform diverse functions through self-reconfiguration, a large-scale form of adaptation. Molecular machines made of modular, reconfigurable components may form the basis for dynamic self-reprogramming in future synthetic cells. To achieve modular reconfiguration in DNA origami assemblies, we previously developed a tile displacement mechanism in which an invader tile replaces another tile in an array with controlled kinetics. Here, we establish design principles for simultaneous reconfigurations in tile assemblies using complex invaders with distinct shapes. We present toehold and branch migration domain configurations that expand the design space of tile displacement reactions by two orders of magnitude. We demonstrate the construction of multitile invaders with fixed and variable sizes and controlled size distributions. We investigate the growth of three-dimensional (3D) barrel structures with variable cross sections and introduce a mechanism for reconfiguring them into 2D structures. Last, we show an example of a sword-shaped assembly transforming into a snake-shaped assembly, illustrating two independent tile displacement reactions occurring concurrently with minimum cross-talk. This work serves as a proof of concept that tile displacement could be a fundamental mechanism for modular reconfiguration robust to temperature and tile concentration.

A Loser-Take-All DNA Circuit.

DNA-based neural networks are a type of DNA circuit capable of molecular pattern recognition tasks. Winner-take-all DNA networks have been developed to scale up the complexity of molecular pattern recognition with a simple molecular implementation. This simplicity was achieved by replacing negative weights in individual neurons with lateral inhibition and competition across neurons, eliminating the need for dual-rail representation. Here we introduce a new type of DNA circuit that is called loser-take-all: an output signal is ON if and only if the corresponding input has the smallest analog value among all inputs. We develop a DNA strand-displacement implementation of loser-take-all circuits that is cascadable without dual-rail representation, maintaining the simplicity desired for scalability. We characterize the impact of effective signal concentrations and reaction rates on the circuit performance, and derive solutions for compensating undesired signal loss and rate differences. Using these approaches, we successfully demonstrate a three-input loser-take-all circuit with nine unique input combinations. Complementary to winner-take-all, loser-take-all DNA circuits could be used for recognition of molecular patterns based on their least similarities to a set of memories, allowing classification decisions for patterns that are extremely noisy. Moreover, the design principle of loser-take-all could be more generally applied in other DNA circuit implementations including k-winner-take-all.