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Published January 18, 2024 | Published
Journal Article Open

Pattern recognition in the nucleation kinetics of non-equilibrium self-assembly

  • 1. ROR icon California Institute of Technology

Abstract

Inspired by biology’s most sophisticated computer, the brain, neural networks constitute a profound reformulation of computational principles1,2,3. Analogous high-dimensional, highly interconnected computational architectures also arise within information-processing molecular systems inside living cells, such as signal transduction cascades and genetic regulatory networks4,5,6,7. Might collective modes analogous to neural computation be found more broadly in other physical and chemical processes, even those that ostensibly play non-information-processing roles? Here we examine nucleation during self-assembly of multicomponent structures, showing that high-dimensional patterns of concentrations can be discriminated and classified in a manner similar to neural network computation. Specifically, we design a set of 917 DNA tiles that can self-assemble in three alternative ways such that competitive nucleation depends sensitively on the extent of colocalization of high-concentration tiles within the three structures. The system was trained in silico to classify a set of 18 grayscale 30 × 30 pixel images into three categories. Experimentally, fluorescence and atomic force microscopy measurements during and after a 150 hour anneal established that all trained images were correctly classified, whereas a test set of image variations probed the robustness of the results. Although slow compared to previous biochemical neural networks, our approach is compact, robust and scalable. Our findings suggest that ubiquitous physical phenomena, such as nucleation, may hold powerful information-processing capabilities when they occur within high-dimensional multicomponent systems.

Copyright and License

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Acknowledgement

We thank M. Brenner, J. Bruck, A. Dinner, D. Doty, D.K. Fygenson, S. Leibler, R.M. Murray, L. Qian, P.W.K. Rothemund, P. Šulc, C. Thachuk, G. Tikhomirov, D. Woods and Z. Zeravcic. T. Zhu, T. Ouldridge, S. Buse, M. Alexander, M. Misra and A. Lapteva also provided valuable feedback on early drafts. We thank Z. Zeravcic for assistance with artwork in Fig. 1. Funding: supported by National Science Foundation grant nos. CCF-1317694 and CCF/FET-2008589, the Evans Foundation for Molecular Medicine, European Research Council grant no. 772766, Science Foundation Ireland grant no. 18/ERCS/5746 and the Carver Mead New Adventures Fund. J.O.B. and A.M. were primarily supported by the University of Chicago Materials Research Science and Engineering Center, which is funded by National Science Foundation under award number DMR-2011854. A.M. acknowledges support from the Simons Foundation.

Contributions

C.G.E., E.W. and A.M. conceived the study. C.G.E. and E.W. designed the molecules. C.G.E., J.O.B., E.W. and A.M. wrote simulation code, designed the experiments and performed the experiments, analysed the data and wrote the manuscript.

Data Availability

AFM images, fluorescence trajectories, DNA sequences and simulation results are available at https://www.dna.caltech.edu/SupplementaryMaterial/MultifariousSST/.

Code Availability

Algorithms for tile set design, sequence design, nucleation rate prediction and pixel-to-tile map optimization are available at https://www.dna.caltech.edu/SupplementaryMaterial/MultifariousSST/.

Conflict of Interest

The authors declare no competing interests.

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Additional details

Created:
January 19, 2024
Modified:
January 19, 2024