Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Engineering of stimuli-responsive lipid-bilayer membranes using supramolecular systems

Nature Reviews Chemistry volume 5, pages 46–61 (2021)Cite this article

Subjects

Abstract

The membrane proteins found in nature control many important cellular functions, including signal transduction and transmembrane ion transport, and these, in turn, are regulated by external stimuli, such as small molecules, membrane potential and light. Membrane proteins also find technological applications in fields ranging from optogenetics to synthetic biology. Synthetic supramolecular analogues have emerged as a complementary method to engineer functional membranes. This Review describes stimuli-responsive supramolecular systems developed for the control of ion transport, signal transduction and catalysis in lipid-bilayer-membrane systems. Recent advances towards achieving spatio-temporal control over activity in artificial and living cells are highlighted. Current challenges, the scope, limitations and future potential to exploit supramolecular systems for engineering stimuli-responsive lipid-bilayer membranes are discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Functional lipid-bilayer membranes using stimuli-responsive supramolecular systems.
Fig. 2: Molecular recognition in lipid-bilayer membranes.
Fig. 3: Photoresponsive synthetic ion-transport systems.
Fig. 4: Ligand-gated synthetic ion channels.
Fig. 5: Mechanosensitive and voltage-sensitive transport systems.
Fig. 6: Non-equilibrium transport systems.
Fig. 7: Synthetic transmembrane signal-transduction systems.

Similar content being viewed by others

References

  1. Yeagle, P. L. The Structure of Biological Membranes (CRC Press, 2011).

  2. Krauss, G. Biochemistry of Signal Transduction and Regulation (Wiley, 2006).

  3. Hauser, A. S. et al. Pharmacogenomics of GPCR drug targets. Cell 172, 41–54.e19 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Miesenböck, G. Optogenetic control of cells and circuits. Annu. Rev. Cell Dev. Biol. 27, 731–758 (2011).

    PubMed  PubMed Central  Google Scholar 

  5. Branton, D. et al. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 26, 1146–1153 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Villar, G., Graham, A. D. & Bayley, H. A tissue-like printed material. Science 340, 48–52 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Elani, Y., Law, R. V. & Ces, O. Vesicle-based artificial cells as chemical microreactors with spatially segregated reaction pathways. Nat. Commun. 5, 5305 (2014).

    CAS  PubMed  Google Scholar 

  8. Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R. & Boyden, E. S. Engineering genetic circuit interactions within and between synthetic minimal cells. Nat. Chem. 9, 431–439 (2017).

    CAS  Google Scholar 

  9. Barba-Bon, A., Nilam, M. & Hennig, A. Supramolecular chemistry in the biomembrane. ChemBioChem 21, 886–910 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Matile, S., Jentzsch, A. V., Montenegro, J. & Fin, A. Recent synthetic transport systems. Chem. Soc. Rev. 40, 2453–2474 (2011).

    CAS  PubMed  Google Scholar 

  11. Barboiu, M. Artificial water channels – incipient innovative developments. Chem. Commun. 52, 5657–5665 (2016).

    CAS  Google Scholar 

  12. Vanuytsel, S., Carniello, J. & Wallace, M. I. Artificial signal transduction across membranes. ChemBioChem 20, 2569–2580 (2019).

    CAS  PubMed  Google Scholar 

  13. Takeuchi, T., Montenegro, J., Hennig, A. & Matile, S. Pattern generation with synthetic sensing systems in lipid bilayer membranes. Chem. Sci. 2, 303–307 (2011).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Matile, S. & Sakai, N. in Analytical Methods in Supramolecular Chemistry (ed. Schalley, C. A.) 711–742 (Wiley, 2012).

  16. Díazde Greñu, B. et al. Synthetic prodiginine obatoclax (GX15-070) and related analogues: anion binding, transmembrane transport, and cytotoxicity properties. Chem. Eur. J. 17, 14074–14083 (2011).

    Google Scholar 

  17. Ko, S.-K. et al. Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells. Nat. Chem. 6, 885–892 (2014).

    CAS  PubMed  Google Scholar 

  18. Li, H. et al. Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia. Nat. Chem. 8, 24–32 (2016).

    CAS  PubMed  Google Scholar 

  19. Busschaert, N. et al. A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations. Nat. Chem. 9, 667–675 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Marsh, D. Thermodynamics of phospholipid self-assembly. Biophys. J. 102, 1079–1087 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kučerka, N., Nieh, M.-P. & Katsaras, J. Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature. Biochim. Biophys. Acta 1808, 2761–2771 (2011).

    PubMed  Google Scholar 

  22. Alenghat, F. J. & Golan, D. E. Membrane protein dynamics and functional implications in mammalian cells. Curr. Top. Membr. 72, 89–120 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3–26 (2001).

    CAS  PubMed  Google Scholar 

  24. Saggiomo, V. et al. The role of lipophilicity in transmembrane anion transport. Chem. Commun. 48, 5274–5276 (2012).

    CAS  Google Scholar 

  25. Busschaert, N. et al. Towards predictable transmembrane transport: QSAR analysis of anion binding and transport. Chem. Sci. 4, 3036–3045 (2013).

    CAS  Google Scholar 

  26. Voskuhl, J. & Ravoo, B. J. Molecular recognition of bilayer vesicles. Chem. Soc. Rev. 38, 495–505 (2009).

    CAS  PubMed  Google Scholar 

  27. Jiang, H. & Smith, B. D. Dynamic molecular recognition on the surface of vesicle membranes. Chem. Commun. 2006, 1407–1409 (2006).

    Google Scholar 

  28. Mammen, M., Choi, S.-K. & Whitesides, G. M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. 37, 2754–2794 (1998).

    Google Scholar 

  29. Doyle, E. L., Hunter, C. A., Phillips, H. C., Webb, S. J. & Williams, N. H. Cooperative binding at lipid bilayer membrane surfaces. J. Am. Chem. Soc. 125, 4593–4599 (2003).

    CAS  PubMed  Google Scholar 

  30. Han, J., Pluhackova, K. & Böckmann, R. A. The multifaceted role of SNARE proteins in membrane fusion. Front. Physiol. 8, 5 (2017).

    PubMed  PubMed Central  Google Scholar 

  31. Gong, Y., Luo, Y. & Bong, D. Membrane activation:  selective vesicle fusion via small molecule recognition. J. Am. Chem. Soc. 128, 14430–14431 (2006).

    CAS  PubMed  Google Scholar 

  32. Ma, M., Gong, Y. & Bong, D. Lipid membrane adhesion and fusion driven by designed, minimally multivalent hydrogen-bonding lipids. J. Am. Chem. Soc. 131, 16919–16926 (2009).

    CAS  PubMed  Google Scholar 

  33. Ma, M. & Bong, D. Controlled fusion of synthetic lipid membrane vesicles. Acc. Chem. Res. 46, 2988–2997 (2013).

    CAS  PubMed  Google Scholar 

  34. Paleos, C. M. & Pantos, A. Molecular recognition and organizational and polyvalent effects in vesicles induce the formation of artificial multicompartment cells as model systems of eukaryotes. Acc. Chem. Res. 47, 1475–1482 (2014).

    CAS  PubMed  Google Scholar 

  35. Richard, A. et al. Fusogenic supramolecular vesicle systems induced by metal ion binding to amphiphilic ligands. Proc. Natl Acad. Sci. USA 101, 15279–15284 (2004).

    CAS  PubMed  Google Scholar 

  36. Haluska, C. K. et al. Time scales of membrane fusion revealed by direct imaging of vesicle fusion with high temporal resolution. Proc. Natl Acad. Sci. USA 103, 15841–15846 (2006).

    CAS  PubMed  Google Scholar 

  37. Mart, R. J., Liem, K. P., Wang, X. & Webb, S. J. The effect of receptor clustering on vesicle–vesicle adhesion. J. Am. Chem. Soc. 128, 14462–14463 (2006).

    CAS  PubMed  Google Scholar 

  38. Gruber, B., Balk, S., Stadlbauer, S. & König, B. Dynamic interface imprinting: high-affinity peptide binding sites assembled by analyte-induced recruiting of membrane receptors. Angew. Chem. Int. Ed. 51, 10060–10063 (2012).

    CAS  Google Scholar 

  39. Gruber, B., Kataev, E., Aschenbrenner, J., Stadlbauer, S. & König, B. Vesicles and micelles from amphiphilic zinc(II)–cyclen complexes as highly potent promoters of hydrolytic DNA cleavage. J. Am. Chem. Soc. 133, 20704–20707 (2011).

    CAS  PubMed  Google Scholar 

  40. Banerjee, S. & König, B. Molecular imprinting of luminescent vesicles. J. Am. Chem. Soc. 135, 2967–2970 (2013).

    CAS  PubMed  Google Scholar 

  41. Gadsby, D. C. Ion channels versus ion pumps: the principal difference, in principle. Nat. Rev. Mol. Cell Biol. 10, 344–352 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Weber, J. Toward the ATP synthase mechanism. Nat. Chem. Biol. 6, 794–795 (2010).

    CAS  PubMed  Google Scholar 

  43. Ernst, O. P. et al. Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem. Rev. 114, 126–163 (2014).

    CAS  PubMed  Google Scholar 

  44. Kanai, R., Ogawa, H., Vilsen, B., Cornelius, F. & Toyoshima, C. Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state. Nature 502, 201–206 (2013).

    CAS  PubMed  Google Scholar 

  45. Bean, B. P. The action potential in mammalian central neurons. Nat. Rev. Neurosci. 8, 451–465 (2007).

    CAS  PubMed  Google Scholar 

  46. Ketchem, R. R., Hu, W. & Cross, T. A. High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. Science 261, 1457–1460 (1993).

    CAS  PubMed  Google Scholar 

  47. Ohkuma, S. et al. Prodigiosins uncouple lysosomal vacuolar-type ATPase through promotion of H+/Cl− symport. Biochem. J. 334, 731–741 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Lehn, J.-M. Toward complex matter: supramolecular chemistry and self-organization. Proc. Natl Acad. Sci. USA 99, 4763–4768 (2002).

    CAS  PubMed  Google Scholar 

  49. Matile, S., Som, A. & Sordé, N. Recent synthetic ion channels and pores. Tetrahedron 60, 6405–6435 (2004).

    CAS  Google Scholar 

  50. Fyles, T. M. Synthetic ion channels in bilayer membranes. Chem. Soc. Rev. 36, 335–347 (2007).

    CAS  PubMed  Google Scholar 

  51. Busschaert, N. & Gale, P. A. Small-molecule lipid-bilayer anion transporters for biological applications. Angew. Chem. Int. Ed. 52, 1374–1382 (2013).

    CAS  Google Scholar 

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

    Article  Google Scholar 

  53. 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).

    CAS  PubMed  Google Scholar 

  54. Alfonso, I. & Quesada, R. Biological activity of synthetic ionophores: ion transporters as prospective drugs? Chem. Sci. 4, 3009–3019 (2013).

    CAS  Google Scholar 

  55. De Riccardis, F., Izzo, I., Montesarchio, D. & Tecilla, P. Ion transport through lipid bilayers by synthetic ionophores: modulation of activity and selectivity. Acc. Chem. Res. 46, 2781–2790 (2013).

    PubMed  Google Scholar 

  56. Wu, X., Gilchrist, A. M. & Gale, P. A. Prospects and challenges in anion recognition and transport. Chem 6, 1296–1309 (2020).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  58. Göpfrich, K. & Keyser, U. F. in Biological and Bio-inspired Nanomaterials: Properties and Assembly Mechanisms (eds Perrett, S., Buell, A. K. & Knowles, T. P. J.) 331–370 (Springer, 2019).

  59. Bae, W., Kocabey, S. & Liedl, T. DNA nanostructures in vitro, in vivo and on membranes. Nano Today 26, 98–107 (2019).

    CAS  Google Scholar 

  60. Velema, W. A., Szymanski, W. & Feringa, B. L. Photopharmacology: beyond proof of principle. J. Am. Chem. Soc. 136, 2178–2191 (2014).

    CAS  PubMed  Google Scholar 

  61. Ellis-Davies, G. C. R. Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat. Methods 4, 619–628 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Koçer, A., Walko, M., Meijberg, W. & Feringa, B. L. A light-actuated nanovalve derived from a channel protein. Science 309, 755–758 (2005).

    PubMed  Google Scholar 

  63. Bao, C., Ma, M., Meng, F., Lin, Q. & Zhu, L. Efficient synthetic supramolecular channels and their light-deactivated ion transport in bilayer lipid membranes. New J. Chem. 39, 6297–6302 (2015).

    CAS  Google Scholar 

  64. Malla, J. A. et al. A glutathione activatable ion channel induces apoptosis in cancer cells by depleting intracellular glutathione levels. Angew. Chem. Int. Ed. 59, 7944–7952 (2020).

    CAS  Google Scholar 

  65. Salunke, S. B., Malla, J. A. & Talukdar, P. Phototriggered release of a transmembrane chloride carrier from an o-nitrobenzyl-linked procarrier. Angew. Chem. Int. Ed. 58, 5354–5358 (2019).

    CAS  Google Scholar 

  66. Fares, M. et al. Stimuli-responsive cycloaurated “OFF-ON” switchable anion transporters. Angew. Chem. Int. Ed. 59, 17614–17621 (2020).

    CAS  Google Scholar 

  67. Russew, M.-M. & Hecht, S. Photoswitches: from molecules to materials. Adv. Mater. 22, 3348–3360 (2010).

    CAS  PubMed  Google Scholar 

  68. Dhammika Bandara, H. M. & C. Burdette, S. Photoisomerization in different classes of azobenzene. Chem. Soc. Rev. 41, 1809–1825 (2012).

    Google Scholar 

  69. Beharry, A. A. & Woolley, G. A. Azobenzene photoswitches for biomolecules. Chem. Soc. Rev. 40, 4422–4437 (2011).

    CAS  PubMed  Google Scholar 

  70. Szymański, W., Beierle, J. M., Kistemaker, H. A. V., Velema, W. A. & Feringa, B. L. Reversible photocontrol of biological systems by the incorporation of molecular photoswitches. Chem. Rev. 113, 6114–6178 (2013).

    PubMed  Google Scholar 

  71. Mart, R. J. & Allemann, R. K. Azobenzene photocontrol of peptides and proteins. Chem. Commun. 52, 12262–12277 (2016).

    CAS  Google Scholar 

  72. Asanuma, H. et al. Synthesis of azobenzene-tethered DNA for reversible photo-regulation of DNA functions: hybridization and transcription. Nat. Protoc. 2, 203–212 (2007).

    CAS  PubMed  Google Scholar 

  73. Szymański, W., Yilmaz, D., Koçer, A. & Feringa, B. L. Bright ion channels and lipid bilayers. Acc. Chem. Res. 46, 2910–2923 (2013).

    PubMed  Google Scholar 

  74. Kuiper, J. M. & Engberts, J. B. F. N. H-aggregation of azobenzene-substituted amphiphiles in vesicular membranes. Langmuir 20, 1152–1160 (2004).

    CAS  PubMed  Google Scholar 

  75. Kuiper, J. M., Stuart, M. C. A. & Engberts, J. B. F. N. Photochemically induced disturbance of the alkyl chain packing in vesicular membranes. Langmuir 24, 426–432 (2008).

    CAS  PubMed  Google Scholar 

  76. Ishii, K. et al. Reversible control of exo- and endo-budding transitions in a photosensitive lipid membrane. ChemBioChem 10, 251–256 (2009).

    CAS  PubMed  Google Scholar 

  77. Beharry, A. A., Sadovski, O. & Woolley, G. A. Azobenzene photoswitching without ultraviolet light. J. Am. Chem. Soc. 133, 19684–19687 (2011).

    CAS  PubMed  Google Scholar 

  78. Bléger, D., Schwarz, J., Brouwer, A. M. & Hecht, S. o -Fluoroazobenzenes as readily synthesized photoswitches offering nearly quantitative two-way isomerization with visible light. J. Am. Chem. Soc. 134, 20597–20600 (2012).

    PubMed  Google Scholar 

  79. Banghart, M., Borges, K., Isacoff, E., Trauner, D. & Kramer, R. H. Light-activated ion channels for remote control of neuronal firing. Nat. Neurosci. 7, 1381–1386 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Fehrentz, T., Schönberger, M. & Trauner, D. Optochemical genetics. Angew. Chem. Int. Ed. 50, 12156–12182 (2011).

    CAS  Google Scholar 

  81. Kramer, R. H., Chambers, J. J. & Trauner, D. Photochemical tools for remote control of ion channels in excitable cells. Nat. Chem. Biol. 1, 360–365 (2005).

    CAS  PubMed  Google Scholar 

  82. Tochitsky, I., Kienzler, M. A., Isacoff, E. & Kramer, R. H. Restoring vision to the blind with chemical photoswitches. Chem. Rev. 118, 10748–10773 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Gorostiza, P. & Isacoff, E. Y. Optical switches for remote and noninvasive control of cell signaling. Science 322, 395–399 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Hüll, K., Morstein, J. & Trauner, D. In vivo photopharmacology. Chem. Rev. 118, 10710–10747 (2018).

    PubMed  Google Scholar 

  85. Lien, L., Jaikaran, D. C. J., Zhang, Z. & Woolley, G. A. Photomodulated blocking of gramicidin ion channels. J. Am. Chem. Soc. 118, 12222–12223 (1996).

    CAS  Google Scholar 

  86. Jog, P. V. & Gin, M. S. A light-gated synthetic ion channel. Org. Lett. 10, 3693–3696 (2008).

    CAS  PubMed  Google Scholar 

  87. Zhou, Y. et al. Reversible photo-gated transmembrane channel assembled from an acylhydrazone-containing crown ether triad. Chem. Commun. 53, 3681–3684 (2017).

    CAS  Google Scholar 

  88. Shinkai, S., Nakaji, T., Ogawa, T., Shigematsu, K. & Manabe, O. Photoresponsive crown ethers. 2. Photocontrol of ion extraction and ion transport by a bis(crown ether) with a butterfly-like motion. J. Am. Chem. Soc. 103, 111–115 (1981).

    CAS  Google Scholar 

  89. Rin Choi, Y. et al. Azobenzene-based chloride transporters with light-controllable activities. Chem. Commun. 50, 15305–15308 (2014).

    Google Scholar 

  90. Ahmed, M., Metya, S., Das, A. & Talukdar, P. A sandwich azobenzene–diamide dimer for photoregulated chloride transport. Chem. Eur. J. 26, 8703–8708 (2020).

    Google Scholar 

  91. Kerckhoffs, A. & Langton, M. Reversible photo-control over transmembrane anion transport using visible-light responsive supramolecular carriers. Chem. Sci. 11, 6325–6331 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. García-López, V. et al. Molecular machines open cell membranes. Nature 548, 567–572 (2017).

    PubMed  Google Scholar 

  93. Koumura, N., Zijlstra, R. W. J., van Delden, R. A., Harada, N. & Feringa, B. L. Light-driven monodirectional molecular rotor. Nature 401, 152–155 (1999).

    CAS  PubMed  Google Scholar 

  94. Kassem, S. et al. Artificial molecular motors. Chem. Soc. Rev. 46, 2592–2621 (2017).

    CAS  PubMed  Google Scholar 

  95. Liu, D. et al. Near-infrared light activates molecular nanomachines to drill into and kill cells. ACS Nano 13, 6813–6823 (2019).

    CAS  PubMed  Google Scholar 

  96. Tedesco, M. M., Ghebremariam, B., Sakai, N. & Matile, S. Modeling the selectivity of potassium channels with synthetic, ligand-assembled π slides. Angew. Chem. Int. Ed. 38, 540–543 (1999).

    CAS  Google Scholar 

  97. Gorteau, V. et al. Synthetic multifunctional pores with external and internal active sites for ligand gating and noncompetitive blockage. J. Am. Chem. Soc. 126, 13592–13593 (2004).

    CAS  PubMed  Google Scholar 

  98. Talukdar, P., Bollot, G., Mareda, J., Sakai, N. & Matile, S. Ligand-gated synthetic ion channels. Chem. Eur. J. 11, 6525–6532 (2005).

    CAS  PubMed  Google Scholar 

  99. Muraoka, T. et al. Reversible ion transportation switch by a ligand-gated synthetic supramolecular ion channel. J. Am. Chem. Soc. 136, 15584–15595 (2014).

    CAS  PubMed  Google Scholar 

  100. P. Wilson, C. & J. Webb, S. Palladium(II)-gated ion channels. Chem. Commun. 34, 4007–4009 (2008).

    Google Scholar 

  101. Devi, U., Brown, J. R. D., Almond, A. & Webb, S. J. Pd(II)-mediated assembly of porphyrin channels in bilayer membranes. Langmuir 27, 1448–1456 (2011).

    CAS  PubMed  Google Scholar 

  102. Zhu, J. et al. Reversible ligand-gated ion channel via the interconversion between hollow single helix and intertwined double helix. Angew. Chem. Int. Ed. 59, 13602–13607 (2020).

    Google Scholar 

  103. Boccalon, M., Iengo, E. & Tecilla, P. Metal–organic transmembrane nanopores. J. Am. Chem. Soc. 134, 20310–20313 (2012).

    CAS  PubMed  Google Scholar 

  104. Haynes, C. J. E. et al. Blockable Zn10L15 ion channels through subcomponent self-assembly. Angew. Chem. Int. Ed. 56, 15388–15392 (2017).

    CAS  Google Scholar 

  105. Haswell, E. S., Phillips, R. & Rees, D. C. Mechanosensitive channels: what can they do and how do they do it? Structure 19, 1356–1369 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Muraoka, T. et al. Mechano-sensitive synthetic ion channels. J. Am. Chem. Soc. 139, 18016–18023 (2017).

    CAS  PubMed  Google Scholar 

  107. Chen, W.-H. & Regen, S. L. Thermally gated liposomes. J. Am. Chem. Soc. 127, 6538–6539 (2005).

    CAS  PubMed  Google Scholar 

  108. Danial, M., Tran, C. M.-N., Jolliffe, K. A. & Perrier, S. Thermal gating in lipid membranes using thermoresponsive cyclic peptide–polymer conjugates. J. Am. Chem. Soc. 136, 8018–8026 (2014).

    CAS  PubMed  Google Scholar 

  109. Gouaux, E. & MacKinnon, R. Principles of selective ion transport in channels and pumps. Science 310, 1461–1465 (2005).

    CAS  PubMed  Google Scholar 

  110. Bezanilla, F. The voltage sensor in voltage-dependent ion channels. Physiol. Rev. 80, 555–592 (2000).

    CAS  PubMed  Google Scholar 

  111. Si, W., Li, Z.-T. & Hou, J.-L. Voltage-driven reversible insertion into and leaving from a lipid bilayer: tuning transmembrane transport of artificial channels. Angew. Chem. Int. Ed. 53, 4578–4581 (2014).

    CAS  Google Scholar 

  112. Chen, L. et al. Chiral selective transmembrane transport of amino acids through artificial channels. J. Am. Chem. Soc. 135, 2152–2155 (2013).

    CAS  PubMed  Google Scholar 

  113. Fyles, T. M., Loock, D. & Zhou, X. A voltage-gated ion channel based on a bis-macrocyclic bolaamphiphile. J. Am. Chem. Soc. 120, 2997–3003 (1998).

    CAS  Google Scholar 

  114. Goto, C., Yamamura, M., Satake, A. & Kobuke, Y. Artificial ion channels showing rectified current behavior. J. Am. Chem. Soc. 123, 12152–12159 (2001).

    CAS  PubMed  Google Scholar 

  115. Sakai, N., Gerard, D. & Matile, S. Electrostatics of cell membrane recognition:  structure and activity of neutral and cationic rigid push-pull rods in isoelectric, anionic, and polarized lipid bilayer membranes. J. Am. Chem. Soc. 123, 2517–2524 (2001).

    CAS  PubMed  Google Scholar 

  116. Wu, X. et al. Voltage-switchable HCl transport enabled by lipid headgroup–transporter interactions. Angew. Chem. Int. Ed. 58, 15142–15147 (2019).

    CAS  Google Scholar 

  117. Busschaert, N. et al. Thiosquaramides: pH switchable anion transporters. Chem. Sci. 5, 3617–3626 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Elmes, R. B. P., Busschaert, N., Czech, D. D., Gale, P. A. & Jolliffe, K. A. pH switchable anion transport by an oxothiosquaramide. Chem. Commun. 51, 10107–10110 (2015).

    CAS  Google Scholar 

  119. Hernando, E. et al. Small molecule anionophores promote transmembrane anion permeation matching CFTR activity. Sci. Rep. 8, 2608 (2018).

    PubMed  PubMed Central  Google Scholar 

  120. Biswas, O. et al. Chloride ion transport by PITENINs across the phospholipid bilayers of vesicles and cells. ACS Appl. Bio Mater. 3, 935–944 (2020).

    CAS  Google Scholar 

  121. Choi, Y. R., Lee, B., Park, J., Namkung, W. & Jeong, K.-S. Enzyme-responsive procarriers capable of transporting chloride ions across lipid and cellular membranes. J. Am. Chem. Soc. 138, 15319–15322 (2016).

    CAS  PubMed  Google Scholar 

  122. Mann, S. Life as a nanoscale phenomenon. Angew. Chem. Int. Ed. 47, 5306–5320 (2008).

    CAS  Google Scholar 

  123. van Rossum, S. A. P., Tena-Solsona, M., van Esch, J. H., Eelkema, R. & Boekhoven, J. Dissipative out-of-equilibrium assembly of man-made supramolecular materials. Chem. Soc. Rev. 46, 5519–5535 (2017).

    PubMed  Google Scholar 

  124. Boekhoven, J., Hendriksen, W. E., Koper, G. J. M., Eelkema, R. & van Esch, J. H. Transient assembly of active materials fueled by a chemical reaction. Science 349, 1075–1079 (2015).

    CAS  PubMed  Google Scholar 

  125. Maiti, S., Fortunati, I., Ferrante, C., Scrimin, P. & Prins, L. J. Dissipative self-assembly of vesicular nanoreactors. Nat. Chem. 8, 725–731 (2016).

    CAS  PubMed  Google Scholar 

  126. della Sala, F., Maiti, S., Bonanni, A., Scrimin, P. & Prins, L. J. Fuel-selective transient activation of nanosystems for signal generation. Angew. Chem. Int. Ed. 57, 1611–1615 (2018).

    Google Scholar 

  127. Biagini, C. et al. Dissipative catalysis with a molecular machine. Angew. Chem. Int. Ed. 58, 9876–9880 (2019).

    CAS  Google Scholar 

  128. Bennett, I. M. et al. Active transport of Ca2+ by an artificial photosynthetic membrane. Nature 420, 398–401 (2002).

    CAS  PubMed  Google Scholar 

  129. Steinberg-Yfrach, G. et al. Conversion of light energy to proton potential in liposomes by artificial photosynthetic reaction centres. Nature 385, 239–241 (1997).

    CAS  Google Scholar 

  130. Steinberg-Yfrach, G. et al. Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial photosynthetic membrane. Nature 392, 479–482 (1998).

    CAS  PubMed  Google Scholar 

  131. Bhosale, S. et al. Photoproduction of proton gradients with π-stacked fluorophore scaffolds in lipid bilayers. Science 313, 84–86 (2006).

    CAS  PubMed  Google Scholar 

  132. Howe, E. N. W. & Gale, P. A. Fatty acid fueled transmembrane chloride transport. J. Am. Chem. Soc. 141, 10654–10660 (2019).

    CAS  PubMed  Google Scholar 

  133. Dambenieks, A. K., Vu, P. H. Q. & Fyles, T. M. Dissipative assembly of a membrane transport system. Chem. Sci. 5, 3396–3403 (2014).

    CAS  Google Scholar 

  134. Simon, M. I., Strathmann, M. P. & Gautam, N. Diversity of G proteins in signal transduction. Science 252, 802–808 (1991).

    CAS  PubMed  Google Scholar 

  135. Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 103, 211–225 (2000).

    CAS  PubMed  Google Scholar 

  136. Kikuchi, J.-I. & Murakami, Y. Steroid cyclophanes as artificial cell-surface receptors. Molecular recognition and its consequence in signal transduction behavior. J. Incl. Phenom. Mol. Recognit. Chem. 32, 209–221 (1998).

    CAS  Google Scholar 

  137. Kikuchi, J., Ariga, K., Sasaki, Y. & Ikeda, K. Control of enzymic activity by artificial cell-surface receptors. J. Mol. Catal. B Enzym. 11, 977–984 (2001).

    CAS  Google Scholar 

  138. Tian, W.-J., Sasaki, Y., Fan, S.-D. & Kikuchi, J.-I. Switching of enzymatic activity through functional connection of molecular recognition on lipid bilayer membranes. Supramol. Chem. 17, 113–119 (2005).

    CAS  Google Scholar 

  139. Kikuchi, J., Ariga, K. & Ikeda, K. Signal transduction mediated by artificial cell-surface receptors: activation of lactate dehydrogenase triggered by molecular recognition and phase reorganization of bile acid derivatives embedded in a synthetic bilayer membrane. Chem. Commun. 1999, 547–548 (1999).

    Google Scholar 

  140. Mukai, M. et al. Propagation and amplification of molecular information using a photoresponsive molecular switch. Supramol. Chem. 21, 284–291 (2009).

    CAS  Google Scholar 

  141. Barton, P., Hunter, C. A., Potter, T. J., Webb, S. J. & Williams, N. H. Transmembrane signalling. Angew. Chem. Int. Ed. 41, 3878–3881 (2002).

    CAS  Google Scholar 

  142. Dijkstra, H. P. et al. Transmission of binding information across lipid bilayers. Chem. Eur. J. 13, 7215–7222 (2007).

    CAS  PubMed  Google Scholar 

  143. Bernitzki, K. & Schrader, T. Entirely artificial signal transduction with a primary messenger. Angew. Chem. Int. Ed. 48, 8001–8005 (2009).

    CAS  Google Scholar 

  144. Bernitzki, K., Maue, M. & Schrader, T. Artificial signal transduction with primary and secondary messengers. Chem. Eur. J. 18, 13412–13417 (2012).

    CAS  PubMed  Google Scholar 

  145. Brioche, J. et al. Conformational switching of a foldamer in a multicomponent system by pH-filtered selection between competing noncovalent interactions. J. Am. Chem. Soc. 137, 6680–6691 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Eccles, N. et al. Remote conformational responses to enantiomeric excess in carboxylate-binding dynamic foldamers. Chem. Commun. 55, 9331–9334 (2019).

    CAS  Google Scholar 

  147. De Poli, M. et al. Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayer. Science 352, 575–580 (2016).

    PubMed  Google Scholar 

  148. Lister, F. G. A., Le Bailly, B. A. F., Webb, S. J. & Clayden, J. Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. Nat. Chem. 9, 420–425 (2017).

    CAS  Google Scholar 

  149. Langton, M. J., Keymeulen, F., Ciaccia, M., Williams, N. H. & Hunter, C. A. Controlled membrane translocation provides a mechanism for signal transduction and amplification. Nat. Chem. 9, 426–430 (2017).

    CAS  PubMed  Google Scholar 

  150. Langton, M. J., Williams, N. H. & Hunter, C. A. Recognition-controlled membrane translocation for signal transduction across lipid bilayers. J. Am. Chem. Soc. 139, 6461–6466 (2017).

    CAS  PubMed  Google Scholar 

  151. Langton, M. J., Scriven, L. M., Williams, N. H. & Hunter, C. A. Triggered release from lipid bilayer vesicles by an artificial transmembrane signal transduction system. J. Am. Chem. Soc. 139, 15768–15773 (2017).

    CAS  PubMed  Google Scholar 

  152. Ding, Y., Williams, N. H. & Hunter, C. A. A synthetic vesicle-to-vesicle communication system. J. Am. Chem. Soc. 141, 17847–17853 (2019).

    CAS  PubMed  Google Scholar 

  153. Mora, N. L. et al. Targeted anion transporter delivery by coiled-coil driven membrane fusion. Chem. Sci. 7, 1768–1772 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Bayley, H. et al. Droplet interface bilayers. Mol. Biosyst. 4, 1191–1208 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Chen, S. et al. An artificial molecular shuttle operates in lipid bilayers for ion transport. J. Am. Chem. Soc. 140, 17992–17998 (2018).

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  157. Ye, R. et al. Molecular ion fishers as highly active and exceptionally selective K+ transporters. J. Am. Chem. Soc. 141, 9788–9792 (2019).

    CAS  PubMed  Google Scholar 

  158. Jentzsch, A. V. et al. Transmembrane anion transport mediated by halogen-bond donors. Nat. Commun. 3, 905 (2012).

    PubMed  Google Scholar 

  159. Benz, S. et al. Anion transport with chalcogen bonds. J. Am. Chem. Soc. 138, 9093–9096 (2016).

    CAS  PubMed  Google Scholar 

  160. Lee, L. M. et al. Anion transport with pnictogen bonds in direct comparison with chalcogen and halogen bonds. J. Am. Chem. Soc. 141, 810–814 (2019).

    CAS  PubMed  Google Scholar 

  161. Bickerton, L. E., Sterling, A. J., Beer, P. D., Duarte, F. & Langton, M. J. Transmembrane anion transport mediated by halogen bonding and hydrogen bonding triazole anionophores. Chem. Sci. 11, 4722–4729 (2020).

    CAS  Google Scholar 

Download references

Acknowledgements

M.J.L. is grateful for funding through a Royal Society University Research Fellowship.

Author information

Authors and Affiliations

  1. Chemistry Research Laboratory, University of Oxford, Oxford, UK

    Matthew J. Langton

Authors
  1. Matthew J. Langton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew J. Langton.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Peer review information

Nature Reviews Chemistry thanks the anonymous reviewers for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Transmembrane signal transduction

The transmission of molecular signals and information across a membrane, typically occurring without the signalling molecule crossing the membrane itself, maintaining cellular compartmentalization.

Stimuli-responsive supramolecular systems

Synthetic molecules or molecular assemblies that exploit intermolecular interactions for their function, and their activity is regulated by changes in their chemical or physical environment.

Mobile ion carriers

Lipid-soluble ion receptors (ionophores) that facilitate transmembrane ion transport by shuttling ions across the membrane.

Photocaging

The use of photolabile protecting groups to temporarily mask the activity of a molecule. Subsequent photoirradiation removes the protecting group to reveal the functional molecule.

Molecular photoswitches

Molecules that can be reversibly switched between at least two distinct states, which acquire different chemical and/or physical properties by absorbing photons.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Langton, M.J. Engineering of stimuli-responsive lipid-bilayer membranes using supramolecular systems. Nat Rev Chem 5, 46–61 (2021). https://doi.org/10.1038/s41570-020-00233-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-020-00233-6

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing