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Autonomous molecular cascades for evaluation of cell surfaces

Nature Nanotechnology volume 8, pages 580–586 (2013)Cite this article

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Abstract

Molecular automata are mixtures of molecules that undergo precisely defined structural changes in response to sequential interactions with inputs1,2,3,4. Previously studied nucleic acid-based automata include game-playing molecular devices (MAYA automata3,5) and finite-state automata for the analysis of nucleic acids6, with the latter inspiring circuits for the analysis of RNA species inside cells7,8. Here, we describe automata based on strand-displacement9,10 cascades directed by antibodies that can analyse cells by using their surface markers as inputs. The final output of a molecular automaton that successfully completes its analysis is the presence of a unique molecular tag on the cell surface of a specific subpopulation of lymphocytes within human blood cells.

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Figure 1: Design considerations for automata operating on cell surfaces.
Figure 2: Demonstration of automata assessing the presence of two cell-surface markers.
Figure 3: Demonstration of automata assessing the absence of a cell-surface marker.
Figure 4: Demonstration of automata assessing the presence of three markers (CD45, CD3 and CD8) on the surface of the cell.
Figure 5: Demonstrations of the potential for practical applications.

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Acknowledgements

The research presented in this manuscript, as well as past attempts that eventually led to the current design, was supported by the National Institutes of Health (R21CA128452, RC2CA147925, R21EB014477 and RGM104960, to S.R. and M.N.S.), the National Science Foundation (CCF-0218262, CCF-0621600, ECCS-1026591 and CBET-1033288), the National Aeronautics and Space Administration (NAS2-02039), and a fellowship from the Lymphoma and Leukemia Foundation (CPD Award) to M.N.S. The authors thank J. Loeb, E. Meffre and D. Stefanovic for their advice and comments on the manuscript.

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Author notes

  1. Maria Rudchenko and Steven Taylor: These authors contributed equally to this work

Authors and Affiliations

  1. Research Division, Hospital for Special Surgery, 535E 70th Street, New York, 10021, New York, USA

    Maria Rudchenko, Steven Taylor, Alesia Dechkovskaia & Sergei Rudchenko

  2. Department of Medicine, Columbia University, 630W 168th Street, New York, 10032, New York, USA

    Payal Pallavi, Safana Khan, Vincent P. Butler Jr, Sergei Rudchenko & Milan N. Stojanovic

  3. Departments of Biomedical Engineering and Systems Biology, Columbia University, 630W 168th Street, New York, 10032, New York, USA

    Milan N. Stojanovic

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  1. Maria Rudchenko
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  7. Sergei Rudchenko
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  8. Milan N. Stojanovic
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Contributions

M.R. and S.T. are considered equal first authors. M.R. was the principal experimenter on cells, and S.T. carried out conjugations and optimized cascades in the solution phase. P.P. performed exploratory experiments. A.D. and S.K. carried out model experiments on beads. S.R. was in charge of flow cytometry experiments, and S.T. and M.N.S. were in charge of non-cell-based experiments. M.N.S. and V.B. designed and suggested early proposals for the implementation of molecular computing on cell surfaces and settled on lymphocytes as targets. M.R., S.T., S.R. and M.N.S. analysed the data. S.R. and M.N.S. were the primary designers of the experiments and are most responsible for the structure of the presentation in this paper. M.N.S. wrote the initial draft of the manuscript.

Corresponding authors

Correspondence to Sergei Rudchenko or Milan N. Stojanovic.

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The authors declare no competing financial interests.

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Rudchenko, M., Taylor, S., Pallavi, P. et al. Autonomous molecular cascades for evaluation of cell surfaces. Nature Nanotech 8, 580–586 (2013). https://doi.org/10.1038/nnano.2013.142

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