Diverse and robust molecular algorithms using reprogrammable DNA self-assembly

• Published in: Nature (London) Vol. 567; no. 7748; pp. 366 - 372
• Main Authors: Woods, Damien, Doty, David, Myhrvold, Cameron, Hui, Joy, Zhou, Felix, Yin, Peng, Winfree, Erik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2019; Nature Publishing Group
• Subjects: 639/705/117; 639/925/926/1047; Algorithms; Automata theory; Biophysics; Cellular automata; Classification; Complexity; Computer simulation; Copying; Counting; Crystallization; Deoxyribonucleic acid; DNA; EDTA; Fabrication; Humanities and Social Sciences; Information processing; Information technology; International conferences; Letter; Mathematical models; Mathematical research; Molecular biology; Molecular interactions; Molecular machines; Molecular modelling; multidisciplinary; Nanotechnology; Organic chemistry; Palindromes; Robots; Robustness (mathematics); Science; Science (multidisciplinary); Self-assembly; Sorting algorithms; Statistical analysis; Systems design; Technology; Tiling
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-1014-9

Molecular biology provides an inspiring proof-of-principle that chemical systems can store and process information to direct molecular activities such as the fabrication of complex structures from molecular components. To develop information-based chemistry as a technology for programming matter to function in ways not seen in biological systems, it is necessary to understand how molecular interactions can encode and execute algorithms. The self-assembly of relatively simple units into complex products 1 is particularly well suited for such investigations. Theory that combines mathematical tiling and statistical–mechanical models of molecular crystallization has shown that algorithmic behaviour can be embedded within molecular self-assembly processes 2 , 3 , and this has been experimentally demonstrated using DNA nanotechnology 4 with up to 22 tile types 5 – 11 . However, many information technologies exhibit a complexity threshold—such as the minimum transistor count needed for a general-purpose computer—beyond which the power of a reprogrammable system increases qualitatively, and it has been unclear whether the biophysics of DNA self-assembly allows that threshold to be exceeded. Here we report the design and experimental validation of a DNA tile set that contains 355 single-stranded tiles and can, through simple tile selection, be reprogrammed to implement a wide variety of 6-bit algorithms. We use this set to construct 21 circuits that execute algorithms including copying, sorting, recognizing palindromes and multiples of 3, random walking, obtaining an unbiased choice from a biased random source, electing a leader, simulating cellular automata, generating deterministic and randomized patterns, and counting to 63, with an overall per-tile error rate of less than 1 in 3,000. These findings suggest that molecular self-assembly could be a reliable algorithmic component within programmable chemical systems. The development of molecular machines that are reprogrammable—at a high level of abstraction and thus without requiring knowledge of the underlying physics—will establish a creative space in which molecular programmers can flourish. A set of 355 self-assembling DNA ‘tiles’ can be reprogrammed to implement many different computer algorithms—including sorting, palindrome testing and divisibility by three—suggesting that molecular self-assembly could be a reliable algorithmic component in programmable chemical systems.