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

Nature Nanotechnology volume 17, pages 514–523 (2022)Cite this article

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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.

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Data availability

Raw data acquisitions for Figs. 2–6, 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_.

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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

  1. Department of Chemistry, Emory University, Atlanta, GA, USA

    Selma Piranej, Alisina Bazrafshan & Khalid Salaita

  2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

    Khalid Salaita

Authors
  1. Selma Piranej
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  2. Alisina Bazrafshan
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  3. Khalid Salaita
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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.

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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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