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Chemical-to-mechanical molecular computation using DNA-based motors with onboard logic

Abstract

DNA has become the biomolecule of choice for molecular computation that may one day complement conventional silicon-based processors. In general, DNA computation is conducted in individual tubes, is slow in generating chemical outputs in response to chemical inputs and requires fluorescence readout. Here, we introduce a new paradigm for DNA computation where the chemical input is processed and transduced into a mechanical output using dynamic DNA-based motors operating far from equilibrium. We show that DNA-based motors with onboard logic (DMOLs) can perform Boolean functions (NOT, YES, AND and OR) with 15 min readout times. Because DMOLs are micrometre-sized, massive arrays of DMOLs that are identical or uniquely encoded by size and refractive index can be multiplexed and perform motor-to-motor communication on the same chip. Finally, DMOL computational outputs can be detected using a conventional smartphone camera, thus transducing chemical information into the electronic domain in a facile manner, suggesting potential applications.

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Fig. 1: Schematic of DMOLs detecting the presence of a chemical input.
Fig. 2: Computation of NOT and YES gates.
Fig. 3: Computation of AND gate.
Fig. 4: Computation of OR gate.
Fig. 5: Encoding DMOLs to multiplex and demonstrate communication.
Fig. 6: Size and material encoded DMOLs.

Data availability

Raw data acquisitions for Figs. 26, S3, S5, S6, and S10 can be found at https://doi.org/10.15139/S3/ZKRS8Z. Additional datasets generated in this study are available from the corresponding author upon reasonable request. Source data are provided with this paper.

Code availability

Python script from bright-field acquisition data regarding net displacements and particle ensemble trajectories can be found at https://github.com/spiranej/particle_tracking_.

References

  1. Wadhams, G. H. & Armitage, J. P. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol. 5, 1024–1037 (2004).

    CAS  Article  Google Scholar 

  2. Srinivas, N. et al. On the biophysics and kinetics of toehold-mediated DNA strand displacement. Nucleic Acids Res. 41, 10641–10658 (2013).

    CAS  Article  Google Scholar 

  3. Genot, A. J., Zhang, D. Y., Bath, J. & Turberfield, A. J. Remote toehold: a mechanism for flexible control of DNA hybridization kinetics. J. Am. Chem. Soc. 133, 2177–2182 (2011).

    CAS  Article  Google Scholar 

  4. Yurke, B., Turberfield, A. J., Mills, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).

    CAS  Article  Google Scholar 

  5. Zhang, D. Y. & Seelig, G. Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3, 103–113 (2011).

    CAS  Article  Google Scholar 

  6. Dirks, R. M. & Pierce, N. A. Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–15278 (2004).

    CAS  Article  Google Scholar 

  7. Augspurger, E. E., Rana, M. & Yigit, M. V. Chemical and biological sensing using hybridization chain reaction. ACS Sens. 3, 878–902 (2018).

    CAS  Article  Google Scholar 

  8. Ge, Z. et al. Hybridization chain reaction amplification of microRNA detection with a tetrahedral DNA nanostructure-based electrochemical biosensor. Anal. Chem. 86, 2124–2130 (2014).

    CAS  Article  Google Scholar 

  9. Bi, S., Chen, M., Jia, X., Dong, Y. & Wang, Z. Hyperbranched hybridization chain reaction for triggered signal amplification and concatenated logic circuits. Angew. Chem. Int. Ed. 54, 8144–8148 (2015).

    CAS  Article  Google Scholar 

  10. Qian, L. & Winfree, E. A simple DNA gate motif for synthesizing large-scale circuits. J. R. Soc. Interface 8, 1281–1297 (2011).

    CAS  Article  Google Scholar 

  11. Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011).

    CAS  Article  Google Scholar 

  12. Song, X., Eshra, A., Dwyer, C. & Reif, J. Renewable DNA seesaw logic circuits enabled by photoregulation of toehold-mediated strand displacement. RSC Adv. 7, 28130–28144 (2017).

    CAS  Article  Google Scholar 

  13. Benenson, Y. et al. Programmable and autonomous computing machine made of biomolecules. Nature 414, 430–434 (2001).

    CAS  Article  Google Scholar 

  14. Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).

    CAS  Article  Google Scholar 

  15. Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, eaan6558 (2017).

    Article  Google Scholar 

  16. Cherry, K. M. & Qian, L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 559, 370–376 (2018).

    CAS  Article  Google Scholar 

  17. Zhou, C., Geng, H., Wang, P. & Guo, C. Programmable DNA nanoindicator‐based platform for large‐scale square root logic biocomputing. Small 15, 1903489 (2019).

    CAS  Article  Google Scholar 

  18. Benenson, Y. Biomolecular computing systems: principles, progress and potential. Nat. Rev. Genet. 13, 455–468 (2012).

    CAS  Article  Google Scholar 

  19. Wang, F. et al. Implementing digital computing with DNA-based switching circuits. Nat. Commun. 11, 121 (2020).

    Article  Google Scholar 

  20. Wang, K. et al. Autonomous DNA nanomachine based on cascade amplification of strand displacement and DNA walker for detection of multiple DNAs. Biosens. Bioelectron. 105, 159–165 (2018).

    CAS  Article  Google Scholar 

  21. You, M., Zhu, G., Chen, T., Donovan, M. J. & Tan, W. Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy. J. Am. Chem. Soc. 137, 667–674 (2015).

    CAS  Article  Google Scholar 

  22. Zhu, J., Zhang, L., Zhou, Z., Dong, S. & Wang, E. Aptamer-based sensing platform using three-way DNA junction-driven strand displacement and its application in DNA logic circuit. Anal. Chem. 86, 312–316 (2014).

    CAS  Article  Google Scholar 

  23. Chen, Y. et al. A DNA logic gate based on strand displacement reaction and rolling circle amplification, responding to multiple low-abundance DNA fragment input signals, and its application in detecting miRNAs. Chem. Commun. 51, 6980–6983 (2015).

    CAS  Article  Google Scholar 

  24. Song, T. et al. Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase. Nat. Nanotechnol. 14, 1075–1081 (2019).

    CAS  Article  Google Scholar 

  25. Shah, S. et al. Using strand displacing polymerase to program chemical reaction networks. J. Am. Chem. Soc. 21, 9587–9593 (2020).

    Google Scholar 

  26. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

    CAS  Article  Google Scholar 

  27. Kang, H. et al. DNA dynamics and computation based on toehold-free strand displacement. Nat. Commun. 12, 4994 (2021).

    CAS  Article  Google Scholar 

  28. Wang, D. et al. Molecular logic gates on DNA origami nanostructures for microRNA diagnostics. Anal. Chem. 86, 1932–1936 (2014).

    CAS  Article  Google Scholar 

  29. Yehl, K. et al. High-speed DNA-based rolling motors powered by RNAseH. Nat. Nanotechnol. 11, 184–190 (2016).

    CAS  Article  Google Scholar 

  30. Bazrafshan, A. et al. Tunable DNA origami motors translocate ballistically over μm distances at nm/s speeds. Angew. Chem. Int. Ed. 59, 9514–9521 (2020).

    CAS  Article  Google Scholar 

  31. Credi, A., Balzani, V., Langford, S. J. & Stoddart, J. F. Logic operations at the molecular level. An XOR gate based on a molecular machine. J. Am. Chem. Soc. 119, 2679–2681 (1997).

    CAS  Article  Google Scholar 

  32. Hu, L., Lu, C.-H. & Willner, I. Switchable catalytic DNA catenanes. Nano Lett. 15, 2099–2103 (2015).

    CAS  Article  Google Scholar 

  33. Blanchard, A. T. et al. Highly polyvalent DNA motors generate 100+ pN of force via autochemophoresis. Nano Lett. 19, 6977–6986 (2019).

    CAS  Article  Google Scholar 

  34. McKinnon, K. M. Flow cytometry: an overview. Curr. Protoc. Immunol. 120, 5.1.1–5.1.11 (2018).

    Article  Google Scholar 

  35. Chatterjee, G., Dalchau, N., Muscat, R. A., Phillips, A. & Seelig, G. A spatially localized architecture for fast and modular DNA computing. Nat. Nanotechnol. 12, 920–927 (2017).

    CAS  Article  Google Scholar 

  36. Vashist, S. K., Mudanyali, O., Schneider, E. M., Zengerle, R. & Ozcan, A. Cellphone-based devices for bioanalytical sciences. Anal. Bioanal. Chem. 406, 3263–3277 (2014).

    CAS  Article  Google Scholar 

  37. Ghonge, T. et al. Smartphone-imaged microfluidic biochip for measuring CD64 expression from whole blood. Analyst 144, 3925–3935 (2019).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We acknowledge support through the following grants: NIH U01AA029345-01, NSF DMR 1905947 and NSF MSN 2004126. We thank S. Urazhdin for access to the thermal evaporator and W. Lam for cellscope.

Author information

Authors and Affiliations

Authors

Contributions

S.P. conceptualized the project, designed all experiments, analysed the data and compiled the figures. A.B. helped in the data analysis and discussion of the data. K.S. conceptualized and supervised the project. S.P. and K.S. wrote the manuscript with contributions from A.B.

Corresponding author

Correspondence to Khalid Salaita.

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The authors declare no competing interests.

Peer review

Peer review information

Nature Nanotechnology thanks Eyal Nir, Zhisong Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–10, Table 1 and captions for Videos 1–7.

Supplementary Video 1

Time-lapse videos of Cy3 (red) and Cy5 (blue) fluorescence channels overlaid, acquired at 5 s intervals for a duration of 15 min. The video was acquired ~30 min after RNaseH addition using a ×100 1.49 NA objective. YES-gated DMOLs modified with 10% staple-lock CED are shown translocating on a 1% surface-lock D* chip after the addition of 1 μM anti-lock DNA. Note that the Cy5 signal gradually bleaches over time. Scale bar, 10 μm.

Supplementary Video 2

Time-lapse videos of Cy3 (red), Cy5 (blue) and FAM (green) fluorescence channels overlaid, acquired at 5 s intervals for a duration of 15 min. The video was acquired ~30 min after RNaseH addition using a ×100 1.49 NA objective. AND-gated DMOLs modified with 50% staple-lock DNA (25% CED and 25% MND) are shown translocating on a 5% surface-lock D* chip after the addition of inputs A + B (1 μm each). Note that the Cy5 and FAM signals gradually bleach over time. Scale bar, 10 μm.

Supplementary Video 3

Time-lapse videos of Cy3 (red), Cy5 (blue) and FAM (green) fluorescence channels overlaid, acquired at 5 s intervals for a duration of 15 min. The video was acquired ~30 min after RNaseH addition using a ×100 1.49 NA objective. DMOL1 (located at the top of the frame) modified with 50% staple-lock CED is shown translocating on a 5% surface-lock DNA chip after the addition of input A. DMOL2 (located at the bottom of the frame) modified with 50% staple-lock (25% CED and 25% MND) is shown stalled on a 5% surface-lock D* chip after the addition of input A as it requires input A + B to unlock and translocate. Note that the Cy5 and FAM signals gradually bleach over time. Scale bar, 10 μm.

Supplementary Video 4

Representative time-lapse bright-field video acquired at 5 s intervals for a duration of 15 min using cellscope. DMOL2 (6 μm polystyrene), DMOL3 (3 μm polystyrene) and DMOL6 (5 μm silica) are shown. DMOLs were added to a 5% surface-lock D* chip and introduced to input A, which rescued the motion of DMOL3. Scale bar, 10 μm.

Supplementary Video 5

Representative time-lapse bright-field video acquired at 5 s intervals for a duration of 15 min using cellscope. DMOL2 (6 μm polystyrene), DMOL3 (3 μm polystyrene) and DMOL6 (5 μm silica) are shown. DMOLs were added to a 5% surface-lock D* chip and introduced to input A + B, which rescued the motion of DMOL2 and DMOL3. Scale bar, 10 μm.

Supplementary Video 6

Representative time-lapse bright-field video acquired at 5 s intervals for a duration of 15 min using cellscope. DMOL2 (6 μm polystyrene), DMOL3 (3 μm polystyrene) and DMOL6 (5 μm silica) are shown. DMOLs were added to a 5% surface-lock D* chip and introduced to input A + B + C, which rescued the motion of DMOL2 and DMOL3. Scale bar, 10 μm.

Supplementary Video 7

Representative time-lapse bright-field video acquired at 5 s intervals for a duration of 15 min using cellscope. DMOL2 (6 μm polystyrene), DMOL3 (3 μm polystyrene) and DMOL6 (5 μm silica) are shown. DMOLs were added to a 5% surface-lock D* chip and introduced to input A + B + C + F, which rescued the motion of DMOL2, DMOL3 and DMOL6. Scale bar, 10 μm.

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Piranej, S., Bazrafshan, A. & Salaita, K. Chemical-to-mechanical molecular computation using DNA-based motors with onboard logic. Nat. Nanotechnol. 17, 514–523 (2022). https://doi.org/10.1038/s41565-022-01080-w

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