journal article·2025-02Open access

Morphology remodelling and membrane channel formation in synthetic cells via reconfigurable DNA nanorafts

Sisi Fan, Shuo Wang, Longjiang Ding, Thomas Speck, Hao Yan, Stephan Nussberger, Na Liu

Nature Materials· Volume 24· Issue 2

Abstract

Abstract The shape of biological matter is central to cell function at different length scales and determines how cellular components recognize, interact and respond to one another. However, their shapes are often transient and hard to reprogramme. Here we construct a synthetic cell model composed of signal-responsive DNA nanorafts, biogenic pores and giant unilamellar vesicles (GUVs). We demonstrate that reshaping of DNA rafts at the nanoscale can be coupled to reshaping of GUVs at the microscale. The nanorafts collectively undergo reversible transitions between isotropic and short-range local order on the lipid membrane, programmably remodelling the GUV shape. Assisted by the biogenic pores, during GUV shape recovery the locally ordered DNA rafts perforate the membrane, forming sealable synthetic channels for large cargo transport. Our work outlines a versatile platform for interfacing reconfigurable DNA nanostructures with synthetic cells, expanding the potential of DNA nanotechnology in synthetic biology.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · Nanopore and Nanochannel Transport Studies · DNA and Nucleic Acid Chemistry

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (54)

Show source-provided references
1. Sezgin, E., Levental, I., Mayor, S. & Eggeling, C. The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat. Rev. Mol. Cell Biol. 18, 361–374 (2017).10.1038/nrm.2017.16 ↗
2. McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005).10.1038/nature04396 ↗
3. Simon, C. et al. Actin dynamics drive cell-like membrane deformation. Nat. Phys. 15, 602–609 (2019).10.1038/s41567-019-0464-1 ↗
4. Farsad, K. & Camilli, P. D. Mechanisms of membrane deformation. Curr. Opin. Cell Biol. 15, 372–381 (2003).10.1016/S0955-0674(03)00073-5 ↗
5. Tanaka, S., Takiguchi, K. & Hayashi, M. Repetitive stretching of giant liposomes utilizing the nematic alignment of confined actin. Commun. Phys. 1, 18 (2018).10.1038/s42005-018-0019-2 ↗
6. Liese, S. & Carlson, A. Membrane shape remodeling by protein crowding. Biophys. J. 120, 2482–2489 (2021).10.1016/j.bpj.2021.04.029 ↗
7. Zimmerberg, J. & Kozlov, M. M. How proteins produce cellular membrane curvature. Nat. Rev. Mol. Cell Biol. 7, 9–19 (2006).10.1038/nrm1784 ↗
8. Baumgart, T., Capraro, B. R., Zhu, C. & Das, S. L. Thermodynamics and mechanics of membrane curvature generation and sensing by proteins and lipids. Annu. Rev. Phys. Chem. 62, 483–506 (2011).10.1146/annurev.physchem.012809.103450 ↗
9. Schwille, P. Bottom-up synthetic biology: engineering in a tinkerer’s world. Science 333, 1252–1254 (2011).10.1126/science.1211701 ↗
10. Schwille, P. & Diez, S. Synthetic biology of minimal systems. Crit. Rev. Biochem. Mol. Biol. 44, 223–242 (2009).10.1080/10409230903074549 ↗
11. Zhan, P., Jahnke, K., Liu, N. & Göpfrich, K. Functional DNA-based cytoskeletons for synthetic cells. Nat. Chem. 14, 958–963 (2022).10.1038/s41557-022-00945-w ↗
12. Kurokawa, C. et al. DNA cytoskeleton for stabilizing artificial cells. Proc. Natl Acad. Sci. USA 114, 7228–7233 (2017).10.1073/pnas.1702208114 ↗
13. Jahnke, K., Huth, V., Mersdorf, U., Liu, N. & Göpfrich, K. Bottom-up assembly of synthetic cells with a DNA cytoskeleton. ACS Nano 16, 7233–7241 (2022).10.1021/acsnano.1c10703 ↗
14. Czogalla, A., Franquelim, H. G. & Schwille, P. DNA nanostructures on membranes as tools for synthetic biology. Biophys. J. 110, 1698–1707 (2016).10.1016/j.bpj.2016.03.015 ↗
15. Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2017).10.1038/natrevmats.2017.68 ↗
16. Dey, S. et al. DNA origami. Nat. Rev. Dis. Prim. 1, 13 (2021).
17. Franquelim, H. G., Khmelinskaia, A., Sobczak, J. P., Dietz, H. & Schwille, P. Membrane sculpting by curved DNA origami scaffolds. Nat. Commun. 9, 811 (2018).10.1038/s41467-018-03198-9 ↗
18. Blood, P. D. & Voth, G. A. Direct observation of Bin/amphiphysin/Rvs (BAR) domain-induced membrane curvature by means of molecular dynamics simulations. Proc. Natl Acad. Sci. USA 103, 15068–15072 (2006).10.1073/pnas.0603917103 ↗
19. Liu, L., Xiong, Q., Xie, C., Pincet, F. & Lin, C. Actuating tension-loaded DNA clamps drives membrane tubulation. Sci. Adv. 8, eadd1830 (2022).10.1126/sciadv.add1830 ↗
20. Birkholz, O. et al. Multi-functional DNA nanostructures that puncture and remodel lipid membranes into hybrid materials. Nat. Commun. 9, 1521 (2018).10.1038/s41467-018-02905-w ↗
21. Czogalla, A. et al. Amphipathic DNA origami nanoparticles to scaffold and deform lipid membrane vesicles. Angew. Chem. Int. Ed. 54, 6501–6505 (2015).10.1002/anie.201501173 ↗
22. De Franceschi, N. et al. Synthetic membrane shaper for controlled liposome deformation. ACS Nano 17, 966–978 (2023).10.1021/acsnano.2c06125 ↗
23. Journot, C. M. A., Ramakrishna, V., Wallace, M. I. & Turberfield, A. J. Modifying membrane morphology and interactions with DNA origami clathrin-mimic networks. ACS Nano 13, 9973–9979 (2019).10.1021/acsnano.8b07734 ↗
24. Franquelim, H. G., Dietz, H. & Schwille, P. Reversible membrane deformations by straight DNA origami filaments. Soft Matter 17, 276–287 (2021).10.1039/D0SM00150C ↗
25. Grome, M. W., Zhang, Z., Pincet, F. & Lin, C. Vesicle tubulation with self-assembling DNA nanosprings. Angew. Chem. Int. Ed. 57, 5330–5334 (2018).10.1002/anie.201800141 ↗
26. Howorka, S. Building membrane nanopores. Nat. Nanotechnol. 12, 619–630 (2017).10.1038/nnano.2017.99 ↗
27. Dey, S. et al. A reversibly gated protein-transporting membrane channel made of DNA. Nat. Commun. 13, 2271 (2022).10.1038/s41467-022-28522-2 ↗
28. Thomsen, R. P. et al. A large size-selective DNA nanopore with sensing applications. Nat. Commun. 10, 5655 (2019).10.1038/s41467-019-13284-1 ↗
29. Xing, Y., Dorey, A., Jayasinghe, L. & Howorka, S. Highly shape- and size-tunable membrane nanopores made with DNA. Nat. Nanotechnol. 17, 708–713 (2022).10.1038/s41565-022-01116-1 ↗
30. Fragasso, A. et al. Reconstitution of ultrawide DNA origami pores in liposomes for transmembrane transport of macromolecules. ACS Nano 15, 12768–12779 (2021).10.1021/acsnano.1c01669 ↗
31. Shen, Q. et al. Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels. Nat. Struct. Mol. Biol. 30, 425–435 (2023).10.1038/s41594-023-00925-9 ↗
32. Shen, Q. et al. Functionalized DNA-origami-protein nanopores generate large transmembrane channels with programmable size-selectivity. J. Am. Chem. Soc. 145, 1292–1300 (2023).10.1021/jacs.2c11226 ↗
33. Shen, Q. et al. DNA-origami nanotrap for studying the selective barriers formed by phenylalanine-glycine-rich nucleoporins. J. Am. Chem. Soc. 143, 12294–12303 (2021).10.1021/jacs.1c05550 ↗
34. Xu, C., Martin, N., Li, M. & Mann, S. Living material assembly of bacteriogenic protocells. Nature 609, 1029–1037 (2022).10.1038/s41586-022-05223-w ↗
35. Degen, M. et al. Structural basis of NINJ1-mediated plasma membrane rupture in cell death. Nature 618, 1065–1071 (2023).10.1038/s41586-023-05991-z ↗
36. Kayagaki, N. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591, 131–136 (2021).10.1038/s41586-021-03218-7 ↗
37. Kayagaki, N. et al. Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury. Nature 618, 1072–1077 (2023).10.1038/s41586-023-06191-5 ↗
38. Kosuri, P., Altheimer, B. D., Dai, M., Yin, P. & Zhuang, X. Rotation tracking of genome-processing enzymes using DNA origami rotors. Nature 572, 136–140 (2019).10.1038/s41586-019-1397-7 ↗
39. Ibusuki, R. et al. Programmable molecular transport achieved by engineering protein motors to move on DNA nanotubes. Science 375, 1159–1164 (2022).10.1126/science.abj5170 ↗
40. Jia, S. et al. Growth and site-specific organization of micron-scale biomolecular devices on living mammalian cells. Nat. Commun. 12, 5729 (2021).10.1038/s41467-021-25890-z ↗
41. Mills, A. et al. A modular spring-loaded actuator for mechanical activation of membrane proteins. Nat. Commun. 13, 3182 (2022).10.1038/s41467-022-30745-2 ↗
42. Donev, A., Burton, J., Stillinger, F. H. & Torquato, S. Tetratic order in the phase behavior of a hard-rectangle system. Phys. Rev. B 73, 054109 (2006).10.1103/PhysRevB.73.054109 ↗
43. Khmelinskaia, A., Franquelim, H. G., Yaadav, R., Petrov, E. P. & Schwille, P. Membrane-mediated self-organization of rod-like DNA origami on supported lipid bilayers. Adv. Mater. Interfaces 8, 2101094 (2021).10.1002/admi.202101094 ↗
44. Stachowiak, J. C. et al. Membrane bending by protein–protein crowding. Nat. Cell Biol. 14, 944–949 (2012).10.1038/ncb2561 ↗
45. Cowan, S. W. et al. Crystal structures explain functional properties of two E. coli porins. Nature 358, 727–733 (1992).10.1038/358727a0 ↗
46. Armstrong, J. K., Wenby, R. B., Meiselman, H. J. & Fisher, T. C. The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation. Biophys. J. 87, 4259–4270 (2004).10.1529/biophysj.104.047746 ↗
47. Lefrançois, P., Goudeau, B. & Arbault, S. Dynamic monitoring of a bi-enzymatic reaction at a single biomimetic giant vesicle. Analyst 145, 7922–7931 (2020).10.1039/D0AN01273D ↗
48. Belluati, A. et al. Artificial cell synthesis using biocatalytic polymerization-induced self-assembly. Nat. Chem. 16, 564–574 (2023).10.1038/s41557-023-01391-y ↗
49. Jang, H.-S., Cho, Y.-K. & Granick, S. Biologically-active unilamellar vesicles from red blood cells. Biomater. Sci. 7, 1393–1398 (2019).10.1039/C8BM01461B ↗
50. Neupert, W. & Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Biochem. 76, 723–749 (2007).10.1146/annurev.biochem.76.052705.163409 ↗
51. Dolezal, P., Likic, V., Tachezy, J. & Lithgow, T. Evolution of the molecular machines for protein import into mitochondria. Science 313, 314–318 (2006).10.1126/science.1127895 ↗
52. Schmick, M. & Bastiaens, P. I. H. The interdependence of membrane shape and cellular signal processing. Cell 156, 1132–1138 (2014).10.1016/j.cell.2014.02.007 ↗
53. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7, 265–275 (2006).10.1038/nrm1890 ↗
54. Wickner, W. & Schekman, R. Protein translocation across biological membranes. Science 310, 1452–1456 (2005).10.1126/science.1113752 ↗