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Foldamer-based ultrapermeable and highly selective artificial water channels that exclude protons

Nature Nanotechnology volume 16, pages 911–917 (2021)Cite this article

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Abstract

The outstanding capacity of aquaporins (AQPs) for mediating highly selective superfast water transport1,2,3,4,5,6,7 has inspired recent development of supramolecular monovalent ion-excluding artificial water channels (AWCs). AWC-based bioinspired membranes are proposed for desalination, water purification and other separation applications8,9,10,11,12,13,14,15,16,17,18. While some recent progress has been made in synthesizing AWCs that approach the water permeability and ion selectivity of AQPs, a hallmark feature of AQPs—high water transport while excluding protons—has not been reproduced. We report a class of biomimetic, helically folded pore-forming polymeric foldamers that can serve as long-sought-after highly selective ultrafast water-conducting channels with performance exceeding those of AQPs (1.1 × 1010 water molecules per second for AQP1), with high water-over-monovalent-ion transport selectivity (~108 water molecules over Cl– ion) conferred by the modularly tunable hydrophobicity of the interior pore surface. The best-performing AWC reported here delivers water transport at an exceptionally high rate, namely, 2.5 times that of AQP1, while concurrently rejecting salts (NaCl and KCl) and even protons.

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Fig. 1: Molecular design and synthesis of foldamer-derived polymer-based synthetic water channels.
Fig. 2: Selective water permeation through foldamer-based polymeric AWCs.
Fig. 3: MD simulations of water transport and mechanism of proton rejection by proton wire breakers created due to presence of fluctuating alkyl groups.

Data availability

The datasets that support the finding of this study are available in figshare repository with the identifier(s) https://figshare.com/s/0354959049b2c0ed4c61. Source data are provided with this paper.

References

  1. Murata, K. et al. Structural determinants of water permeation through aquaporin-1. Nature 407, 599–605 (2000).

    Article  CAS  Google Scholar 

  2. Tajkhorshid, E. et al. Control of the selectivity of the aquaporin water channel family by global orientational tuning. Science 296, 525–530 (2002).

    Article  CAS  Google Scholar 

  3. Takata, K., Matsuzaki, T. & Tajika, Y. Aquaporins: water channel proteins of the cell membrane. Prog. Histochem. Cytochem. 39, 1–83 (2004).

    Article  CAS  Google Scholar 

  4. de Groot, B. L. & Grubmuller, H. Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294, 2353–2357 (2001).

    Article  Google Scholar 

  5. Agre, P. Aquaporin water channels (Nobel lecture). Angew. Chem. Int. Ed. 43, 4278–4290 (2004).

    Article  CAS  Google Scholar 

  6. Borgnia, M. J., Kozono, D., Calamita, G., Maloney, P. C. & Agre, P. Functional reconstitution and characterization of AqpZ, the E. coli water channel protein. J. Mol. Biol. 291, 1169–1179 (1999).

    Article  CAS  Google Scholar 

  7. Horner, A. et al. The mobility of single-file water molecules is governed by the number of H-bonds they may form with channel-lining residues. Sci. Adv. 1, e1400083 (2015).

    Article  Google Scholar 

  8. Fane, A. G., Wang, R. & Hu, M. X. Synthetic membranes for water purification: status and future. Angew. Chem. Int. Ed. 54, 3368–3386 (2015).

    Article  CAS  Google Scholar 

  9. Werber, J. R., Osuji, C. O. & Elimelech, M. Materials for next-generation desalination and water purification membranes. Nat. Rev. Mater. 1, 16018 (2016). https://doi.org/10.1038/natrevmats.2016.18

  10. Park, H. B., Kamcev, J., Robeson, L. M., Elimelech, M. & Freeman, B. D. Maximizing the right stuff: the trade-off between membrane permeability and selectivity. Science 356, eaab0530 (2017).

    Article  CAS  Google Scholar 

  11. Hélix-Nielsen, C. Biomimetic membranes as a technology platform: challenges and opportunities. Membranes 8, 44–59 (2018).

    Article  CAS  Google Scholar 

  12. Werber, J. R. & Elimelech, M. Permselectivity limits of biomimetic desalination membranes. Sci. Adv. 4, eaar8266 (2018).

    Article  CAS  Google Scholar 

  13. Freger, V. Selectivity and polarization in water channel membranes: lessons learned from polymeric membranes and CNTs. Faraday Discuss. 209, 371–388 (2018).

    Article  CAS  Google Scholar 

  14. Wagh, P. & Escobar, I. C. Biomimetic and bioinspired membranes for water purification: a critical review and future directions. Environ. Prog. Sustainable Energy 38, e13215 (2019).

  15. Barboiu, M. & Gilles, A. From natural to bioassisted and biomimetic artificial water channel systems. Acc. Chem. Res. 46, 2814–2823 (2013).

    Article  CAS  Google Scholar 

  16. Huo, Y. P. & Zeng, H. Q. ‘Sticky’-ends-guided creation of functional hollow nanopores for guest encapsulation and water transport. Acc. Chem. Res. 49, 922–930 (2016).

    Article  CAS  Google Scholar 

  17. Gong, B. Artificial water channels: inspiration, progress, and challenges. Faraday Discuss. 209, 415–427 (2018).

    Article  CAS  Google Scholar 

  18. Song, W. & Kumar, M. Artificial water channels: toward and beyond desalination. Curr. Opin. Chem. Eng. 25, 9–17 (2019).

    Article  Google Scholar 

  19. Bhushan, B. Biomimetics: lessons from nature–an overview. Phil. Trans. R. Soc. A 367, 1445–1486 (2009).

    Article  CAS  Google Scholar 

  20. Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998).

    Article  CAS  Google Scholar 

  21. Yu, F. H. & Catterall, W. A. Overview of the voltage-gated sodium channel family. Genome Biol. 4, 207 (2003).

    Article  Google Scholar 

  22. Reuter, H. Membranes: a variety of calcium channels. Nature 316, 391 (1985).

    Article  CAS  Google Scholar 

  23. Dutzler, R., Campbell, E. B. & MacKinnon, R. Gating the selectivity filter in ClC chloride channels. Science 300, 108–112 (2003).

    Article  CAS  Google Scholar 

  24. Mould, J. A. et al. Mechanism for proton conduction of the M2 ion channel of influenza A virus. J. Biol. Chem. 275, 8592–8599 (2000).

    Article  CAS  Google Scholar 

  25. Kaucher, M. S. et al. Selective transport of water mediated by porous dendritic dipeptides. J. Am. Chem. Soc. 129, 11698–11699 (2007).

    Article  CAS  Google Scholar 

  26. Zhou, X. B. et al. Self-assembling subnanometer pores with unusual mass-transport properties. Nat. Commun. 3, 949 (2012).

    Article  CAS  Google Scholar 

  27. Hu, C. B., Chen, Z. X., Tang, G. F., Hou, J. L. & Li, Z. T. Single-molecular artificial transmembrane water channels. J. Am. Chem. Soc. 134, 8384–8387 (2012).

    Article  CAS  Google Scholar 

  28. Licsandru, E. et al. Salt-excluding artificial water channels exhibiting enhanced dipolar water and proton translocation. J. Am. Chem. Soc. 138, 5403–5409 (2016).

    Article  CAS  Google Scholar 

  29. Zhao, H. Q., Sheng, S., Hong, Y. H. & Zeng, H. Q. Proton gradient-induced water transport mediated by water wires inside narrow aquapores of aquafoldamer molecules. J. Am. Chem. Soc. 136, 14270–14276 (2014).

    Article  CAS  Google Scholar 

  30. Shen, Y.-X. et al. Highly permeable artificial water channels that can self-assemble into two-dimensional arrays. Proc. Natl Acad. Sci. USA 112, 9810–9815 (2015).

    Article  CAS  Google Scholar 

  31. Song, W. et al. Artificial water channels enable fast and selective water permeation through water-wire networks. Nat. Nanotechnol. 15, 73–79 (2020).

    Article  CAS  Google Scholar 

  32. Shen, J. et al. Polypyridine-based helical amide foldamer channels: rapid transport of water and protons with high ion rejection. Angew. Chem. Int. Ed. 59, 13328–13334 (2020).

  33. Shen, J. et al. Aquafoldmer-based aquaporin-like synthetic water channel. J. Am. Chem. Soc. 142, 10050–10058 (2020).

    Article  CAS  Google Scholar 

  34. Tunuguntla, R. H. et al. Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins. Science 357, 792–796 (2017).

    Article  CAS  Google Scholar 

  35. Gale, P. A., Davis, J. T. & Quesada, R. Anion transport and supramolecular medicinal chemistry. Chem. Soc. Rev. 46, 2497–2519 (2017).

    Article  CAS  Google Scholar 

  36. Sakai, N. & Matile, S. Synthetic ion channels. Langmuir 29, 9031–9040 (2013).

    Article  CAS  Google Scholar 

  37. Si, W., Xin, P., Li, Z.-T. & Hou, J.-L. Tubular unimolecular transmembrane channels: construction strategy and transport activities. Acc. Chem. Res. 48, 1612–1619 (2015).

    Article  CAS  Google Scholar 

  38. Howorka, S. Building membrane nanopores. Nat. Nanotechnol. 12, 619–630 (2017).

    Article  CAS  Google Scholar 

  39. Zheng, S.-P., Huang, L.-B., Sun, Z. & Barboiu, M. Self-assembled artificial ion-channels toward natural selection of functions. Angew. Chem. Int. Ed. 60, https://doi.org/10.1002/anie.201915287 566–597 (2020).

  40. Roy, A. et al. Polyhydrazide-based organic nanotubes as efficient and selective artificial iodide channels. Angew. Chem. Int. Ed. 59, 4806–4813 (2020).

    Article  CAS  Google Scholar 

  41. Tunuguntla, R. H., Allen, F. I., Kim, K., Belliveau, A. & Noy, A. Ultrafast proton transport in sub-1-nm diameter carbon nanotube porins. Nat. Nanotechnol. 11, 639–644 (2016).

    Article  CAS  Google Scholar 

  42. Ren, C. et al. Molecular swings as highly active ion transporters. Angew. Chem. Int. Ed. 58, 8034–8038 (2019).

    Article  CAS  Google Scholar 

  43. Zeng, L. Z., Zhang, H., Wang, T. & Li, T. Enhancing K+ transport activity and selectivity of synthetic K+ channels via electron-donating effects. Chem. Commun. 56, 1211–1214 (2020).

    Article  CAS  Google Scholar 

  44. Chen, F. et al. Pyridine/oxadiazole-based helical foldamer ion channels with exceptionally high K+/Na+ selectivity. Angew. Chem. Int. Ed. 59, 1440–1444 (2020).

    Article  CAS  Google Scholar 

  45. de Groot, B., Frigato, T., Helms, V. & Grubmüller, H. The mechanism of proton exclusion in the aquaporin-1 water channel. J. Mol. Biol. 333, 279–293 (2003).

    Article  CAS  Google Scholar 

  46. Pohl, P., Saparov, S. M., Borgnia, M. J. & Agre, P. Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ. Proc. Natl Acad. Sci. USA 98, 9624–9629 (2001).

    Article  CAS  Google Scholar 

  47. Pham, T. A. et al. Salt solutions in carbon nanotubes: the role of cation–π interactions. J. Phys. Chem. C 120, 7332–7338 (2016).

    Article  CAS  Google Scholar 

  48. Kim, K. et al. Crystal structure and functional characterization of a light-driven chloride pump having an NTQ motif. Nat. Commun. 7, 12677 (2016).

    Article  CAS  Google Scholar 

  49. Ren, C. L. et al. Pore-forming monopeptides as exceptionally active anion channels. J. Am. Chem. Soc. 140, 8817–8826 (2018).

    Article  CAS  Google Scholar 

  50. Kosinska Eriksson, U. et al. Subangstrom resolution X-ray structure details aquaporin-water interactions. Science 340, 1346–1349 (2013).

    Article  CAS  Google Scholar 

  51. Horner, A., Siligan, C., Cornean, A. & Pohl, P. Positively charged residues at the channel mouth boost single-file water flow. Faraday Discuss. 209, 55–65 (2018).

    Article  CAS  Google Scholar 

  52. Ren, C. et al. A halogen bond-mediated highly active artificial chloride channel with high anticancer activity. Chem. Sci. 9, 4044–4051 (2018).

    Article  CAS  Google Scholar 

  53. Chowdhury, R. et al. PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore. Nat. Commun. 9, 3661 (2018).

    Article  CAS  Google Scholar 

  54. Zhang, C., Wu, J., Galli, G. & Gygi, F. Structural and vibrational properties of liquid water from van der Waals density functionals. J. Chem. Theory Comput. 7, 3054–3061 (2011).

    Article  CAS  Google Scholar 

  55. Li, Y. et al. Water-ion permselectivity of narrow-diameter carbon nanotubes. Sci. Adv. 6, eaba9966 (2020).

    Article  CAS  Google Scholar 

  56. Phillips, J. C. et al. Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802 (2005).

    Article  CAS  Google Scholar 

  57. Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092 (1993).

    Article  CAS  Google Scholar 

  58. Feller, S. E., Zhang, Y., Pastor, R. W. & Brooks, B. R. Constant pressure molecular dynamics simulation: the Langevin piston method. J. Chem. Phys. 103, 4613–4621 (1995).

    Article  CAS  Google Scholar 

  59. Martyna, G. J., Tobias, D. J. & Klein, M. L. Constant pressure molecular dynamics algorithms. J. Chem. Phys. 101, 4177–4189 (1994).

    Article  CAS  Google Scholar 

  60. Sindhikara, D. J., Kim, S., Voter, A. F. & Roitberg, A. E. Bad seeds sprout perilous dynamics: stochastic thermostat induced trajectory synchronization in biomolecules. J. Chem. Theory Comput. 5, 1624–1631 (2009).

    Article  CAS  Google Scholar 

  61. Klauda, J. B. et al. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Chem. Phys. B 114, 7830–7843 (2010).

    Article  CAS  Google Scholar 

  62. Miyamoto, S. & Kollman, P. A. Settle: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 13, 952–962 (1992).

    Article  CAS  Google Scholar 

  63. Andersen, H. C. Rattle: A ‘velocity’ version of the shake algorithm for molecular dynamics calculations. J. Comp. Phys. 52, 24–34 (1983).

    Article  CAS  Google Scholar 

  64. Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).

    Article  CAS  Google Scholar 

  65. Roe, D. R. & Cheatham, T. E. III PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9, 3084–3095 (2013).

    Article  CAS  Google Scholar 

  66. Frisch, M.J. et al. Gaussian 16 rev. C.01 (Wallingford CT, 2016).

  67. Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields. J. Comput. Chem. 31, 671–690 (2010).

    CAS  Google Scholar 

  68. Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM‐GUI: a web‐based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).

    Article  CAS  Google Scholar 

  69. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).

    Article  CAS  Google Scholar 

  70. Decker, K. et al. Selective permeability of truncated aquaporin 1 in silico. ACS Biomater. Sci. Eng. 3, 342–348 (2017).

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Institute of Advanced Synthesis, Northwestern Polytechnical University, China; NanoBio Lab (Biomedical Research Council, Agency for Science, Technology and Research, Singapore); the Singapore National Research Foundation under its Environment and Water Research Programme and administered by PUB; the National Science Foundation (USA) under grant no. DMR-1827346; and the National Institutes of Health under grant no. P41-GM104601. The work in M.K.’s lab was supported by the US National Science Foundation under grant nos. CBET 1946392 and CBET 1952295. Supercomputer time was provided through the Early Allocation grant on Frontera (FTA-Chemla), XSEDE Allocation grant no. MCA05S028 and the Blue Waters petascale supercomputer system at the University of Illinois at Urbana–Champaign.

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Author notes

  1. These authors contributed equally: Arundhati Roy, Jie Shen.

Authors and Affiliations

  1. Department of Chemistry, College of Science, Hainan University, Haikou, Hainan, China

    Arundhati Roy, Jie Shen, Ruijuan Ye & Huaqiang Zeng

  2. NanoBio Lab, 31 Biopolis Way, The Nanos, Singapore

    Arundhati Roy, Ning Li & Changliang Ren

  3. Department of Physics and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana–Champaign, Urbana, IL, USA

    Himanshu Joshi & Aleksei Aksimentiev

  4. Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA

    Woochul Song & Yu-Ming Tu

  5. Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, USA

    Ratul Chowdhury

  6. Department of Civil, Architectural and Environmental Engineering, The University of Texas at Austin, Austin, TX, USA

    Manish Kumar

  7. Institute of Advanced Synthesis, Northwestern Polytechnical University, Xi’an, Shaanxi, China

    Huaqiang Zeng

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Contributions

A.R. synthesized polymers 3 and 5 and conducted the water/ion transport study. J.S. synthesized polymer 4 and conducted the water/ion transport study. H.J. and A.A. performed the MD study. W.S., Y.-M.T. and M.K. determined water-over-chloride selectivity and proton transport rates. R.C. and M.K. conducted analysis of proton exclusion simulations. R.Y., N.L. and C.R. performed some ion transport studies. H.Z. conceived the project and wrote the manuscript with inputs from A.R. and M.K. All the authors edited the manuscript.

Corresponding author

Correspondence to Huaqiang Zeng.

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Supplementary information

Supplementary Information

Experimental procedure, Supplementary Schemes 1–3, Tables 1–3, Figs. 1–19 and 1H/13C NMR spectra.

Supplementary Video 1

MD-generated video illustrating how water gets transported across the hollow cavity of channel 3.

Supplementary Video 2

MD-generated video illustrating how water gets transported across the hollow cavity of channel 4.

Supplementary Video 3

MD-generated video illustrating how water gets transported across the hollow cavity of channel 5.

Source data

Source Data Fig. 2

Original data in Excel format.

Source Data Fig. 3

Original data in Excel format.

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Roy, A., Shen, J., Joshi, H. et al. Foldamer-based ultrapermeable and highly selective artificial water channels that exclude protons. Nat. Nanotechnol. 16, 911–917 (2021). https://doi.org/10.1038/s41565-021-00915-2

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