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.

  • Article
  • Published:

Structure deformation and curvature sensing of PIEZO1 in lipid membranes

This article has been updated

Abstract

PIEZO channels respond to piconewton-scale forces to mediate critical physiological and pathophysiological processes1,2,3,4,5. Detergent-solubilized PIEZO channels form bowl-shaped trimers comprising a central ion-conducting pore with an extracellular cap and three curved and non-planar blades with intracellular beams6,7,8,9,10, which may undergo force-induced deformation within lipid membranes11. However, the structures and mechanisms underlying the gating dynamics of PIEZO channels in lipid membranes remain unresolved. Here we determine the curved and flattened structures of PIEZO1 reconstituted in liposome vesicles, directly visualizing the substantial deformability of the PIEZO1–lipid bilayer system and an in-plane areal expansion of approximately 300 nm2 in the flattened structure. The curved structure of PIEZO1 resembles the structure determined from detergent micelles, but has numerous bound phospholipids. By contrast, the flattened structure exhibits membrane tension-induced flattening of the blade, bending of the beam and detaching and rotating of the cap, which could collectively lead to gating of the ion-conducting pathway. On the basis of the measured in-plane membrane area expansion and stiffness constant of PIEZO1 (ref. 11), we calculate a half maximal activation tension of about 1.9 pN nm−1, matching experimentally measured values. Thus, our studies provide a fundamental understanding of how the notable deformability and structural rearrangement of PIEZO1 achieve exquisite mechanosensitivity and unique curvature-based gating in lipid membranes.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Fig. 1: Cryo-EM structure determination of PIEZO1 proteoliposomes and analyses of PIEZO1–membrane deformation.
Fig. 2: Curved and flattened structures of PIEZO1 in liposome vesicles.
Fig. 3: In-plane membrane area expansion of the PIEZO1-membrane system.
Fig. 4: Structural rearrangement from the curved to the flattened structures.

Similar content being viewed by others

Data availability

The coordinates of the curved and flattened PIEZO1 structures derived from proteoliposomes were deposited in the Protein Data Bank under accessions 7WLT and 7WLU, respectively. The corresponding cryo-EM maps were deposited in the Electron Microscopy Data Bank (EMDB) under accessions EMD-32592 and EMD-32593, respectively.

Change history

  • 19 April 2022

    In the version of this article initially published, the color keys in Fig. 2d were reversed after submission. “Pore lipid” should correspond to the yellow color, “Blade lipids” the blue. The caption description remains correct. The changes have been made to the HTML and PDF versions of the article.

References

  1. Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  2. Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lewis, A. H. & Grandl, J. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife 4, e12088 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Xiao, B. Levering mechanically activated Piezo channels for potential pharmacological intervention. Annu. Rev. Pharmacol. Toxicol. 60, 195–218 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Kefauver, J. M., Ward, A. B. & Patapoutian, A. Discoveries in structure and physiology of mechanically activated ion channels. Nature 587, 567–576 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ge, J. et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature 527, 64–69 (2015).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Wang, L. et al. Structure and mechanogating of the mammalian tactile channel PIEZO2. Nature 573, 225–229 (2019).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Zhao, Q. et al. Structure and mechanogating mechanism of the Piezo1 channel. Nature 554, 487–492 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Saotome, K. et al. Structure of the mechanically activated ion channel Piezo1. Nature 554, 481–486 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Guo, Y. R. & MacKinnon, R. Structure-based membrane dome mechanism for Piezo mechanosensitivity. eLife 6, e33660 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lin, Y. C. et al. Force-induced conformational changes in PIEZO1. Nature 573, 230–234 (2019).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jiang, Y., Yang, X., Jiang, J. & Xiao, B. Structural designs and mechanogating mechanisms of the mechanosensitive piezo channels. Trends Biochem. Sci. 46, 472–488 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Li, J. et al. Piezo1 integration of vascular architecture with physiological force. Nature 515, 279–282 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ranade, S. S. et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl Acad. Sci. USA 111, 10347–10352 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jiang, F. et al. The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction. Nat. Commun. 12, 869 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, S. et al. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J. Clin. Invest. 26, 4527–4536 (2016).

    Article  Google Scholar 

  17. Rode, B. et al. Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat. Commun. 8, 350 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun, W. et al. The mechanosensitive Piezo1 channel is required for bone formation. eLife 8, e47454 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cahalan, S. M. et al. Piezo1 links mechanical forces to red blood cell volume. eLife 4, e07370 (2015).

    Article  PubMed Central  Google Scholar 

  20. Solis, A. G. et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 573, 69–74 (2019).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. Marshall, K. L. et al. PIEZO2 in sensory neurons and urothelial cells coordinates urination. Nature 588, 290–295 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nonomura, K. et al. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541, 176–181 (2017).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Ranade, S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121–125 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Woo, S. H. et al. Piezo2 is the principal mechanotransduction channel for proprioception. Nat. Neurosci. 18, 1756–1762 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Woo, S. H. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622–626 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zeng, W. Z. et al. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science 362, 464–467 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chesler, A. T. et al. The role of PIEZO2 in human mechanosensation. New Engl. J. Med. 375, 1355–1364 (2016).

    Article  CAS  PubMed  Google Scholar 

  28. Szczot, M. et al. PIEZO2 mediates injury-induced tactile pain in mice and humans. Sci. Transl. Med. 10, eaat9892 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang, Y. et al. A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat. Commun. 9, 1300 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhao, Q., Zhou, H., Li, X. & Xiao, B. The mechanosensitive Piezo1 channel: a three-bladed propeller-like structure and a lever-like mechanogating mechanism. FEBS J. 286, 2461–2470 (2018).

    Article  CAS  PubMed  Google Scholar 

  32. Geng, J. et al. A plug-and-latch mechanism for gating the mechanosensitive Piezo channel. Neuron 106, 438–451.e436 (2020).

    Article  CAS  PubMed  Google Scholar 

  33. Lewis, A. H. & Grandl, J. Inactivation kinetics and mechanical gating of Piezo1 ion channels depend on subdomains within the cap. Cell Rep. 30, 870–880.e872 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zheng, W., Gracheva, E. O. & Bagriantsev, S. N. A hydrophobic gate in the inner pore helix is the major determinant of inactivation in mechanosensitive Piezo channels. eLife 8, e44003 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  35. De Vecchis, D., Beech, D. J. & Kalli, A. C. Molecular dynamics simulations of Piezo1 channel opening by increases in membrane tension. Biophys. J. 120, 1510–1521 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang, L. & Sigworth, F. J. Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy. Nature 461, 292–295 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yao, X., Fan, X. & Yan, N. Cryo-EM analysis of a membrane protein embedded in the liposome. Proc. Natl Acad. Sci. USA 117, 18497–18503 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Baxa, U. Imaging of liposomes by transmission electron microscopy. Methods Mol. Biol. 1682, 73–88 (2018).

    Article  CAS  PubMed  Google Scholar 

  39. Snijder, J. et al. Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids. J. Struct. Biol. 198, 38–42 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tonggu, L. & Wang, L. Cryo-EM sample preparation method for extremely low concentration liposomes. Ultramicroscopy 208, 112849 (2020).

    Article  CAS  PubMed  Google Scholar 

  41. Lei, J. & Frank, J. Automated acquisition of cryo-electron micrographs for single particle reconstruction on an FEI Tecnai electron microscope. J. Struct. Biol. 150, 69–80 (2005).

    Article  PubMed  Google Scholar 

  42. Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hu, M. et al. A particle-filter framework for robust cryo-EM 3D reconstruction. Nat. Methods 15, 1083–1089 (2018).

    Article  CAS  PubMed  Google Scholar 

  46. Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63–65 (2014).

    Article  CAS  PubMed  Google Scholar 

  47. Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).

    Article  PubMed  Google Scholar 

  48. Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Chen, M. et al. Convolutional neural networks for automated annotation of cellular cryo-electron tomograms. Nat. Methods 14, 983–985 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank H. Wang, N. Liu and J. Xu for providing the graphene grids; C. Yan for sharing the scripts for deep-2D; L. Wang, H. Zhou, X. Yao, X. Fan, J. Lei and X. Li for technical help; T. Zhao and X. Zhang for developing the Epicker software; the Beijing Frontier Research Center for Biological Structure and Beijing Advanced Innovation Center for Structural Biology for facility and financial support; and the Protein Preparation and Identification Facility at Technology Center for Protein Science in Tsinghua University for facility support. This work was supported by grant numbers 2021ZD0203301, 31825014, 32130049, 32021002, 31630090, 2016YFA0500402 and 2015CB910102 to B.X.; 31570730, 2016YFA0501102 and 2016YFA0501902 to X.L.; from either the Ministry of Science and Technology of the People’s Republic of China or the National Natural Science Foundation of China.

Author information

Authors and Affiliations

Authors

Contributions

X.Y. carried out protein purification, proteoliposome reconstitution, cryo-EM sample preparation, data collection, prepared figures and helped with manuscript writing. C.L. performed EM sample preparation, data collection, image processing and model building, and participated in proteoliposome reconstitution. X.C. performed protein purification, proteoliposome reconstitution, cryo-EM sample preparation and data collection. S.L. performed image processing and analysis. X.L. supervised cryo-EM data collection and image processing. B.X. conceived and directed the study, analysed the structure, created figures and wrote the manuscript with help from the other authors.

Corresponding authors

Correspondence to Xueming Li or Bailong Xiao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature thanks Yifan Cheng and the other, anonymous, reviewers for their contribution to the peer review of this work. Peer reviewer reports are available.

Additional information

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

Extended data figures and tables

Extended Data Fig. 1 Optimization of PIEZO1 proteoliposome reconstitution and cryo-EM sample preparation.

a, The 38-TM topological model of PIEZO1 showing the indicated structural domains. THU: Transmembrane Helical Unit. b, A trace of gel filtration of purified PIEZO1 proteins using the detergent C12E10. UV, ultraviolet. Dash lines indicate the peak fractions collected for subsequent studies. c, A negative staining EM image of PIEZO1 purified in C12E10. (Scale bar = 50nm). d, Cryo-EM images of PIEZO1 proteoliposomes using Bio-beads SM-2 for removing the indicated detergents. The white star indicates the aggregation. e and f, Cryo-EM images of PIEZO1 proteoliposomes using either dialysis to remove 2% glyco-diosgenin (GDN) (d) or SEC for decyl maltoside (DM) removal (e). g, Negative staining EM images of the indicated fractions after gradient centrifugation. DM solubilized soy lipid were either mixed with PIEZO1 proteins or the same volume of buffer. After detergent removal, samples were processed into an iodixanol-based gradient centrifugation. h, A Cryo-EM image of liposomes sticking on the carbon film. 4 µl liposome solution was applied to a holey Quantifoil Au grid with a standard 25 s glow discharge pre-treatment. After 30 s incubation, the grid was blotted and plunged into liquid ethane. The image was focused on the border between the hole and carbon film to exhibit the biased liposome distribution. i, 3D segmentation of a constructed tomogram showing PIEZO1 proteoliposomes clustered in the air-water interface instead of diffusion into the water. j, Distributions of PIEZO1 proteoliposomes on Quantifoil Au grids treated with different glow discharge time. The cryo-samples were prepared by multi-application method descried in Method, and prolonged glow-discharge time facilitated the abundant distribution of liposomes in the hole area suitable for cryo-EM imaging.

Extended Data Fig. 2 Analyses of the deformation of the PIEZO1 proteoliposomes.

a, Cryo-EM micrograph of PIEZO1 proteoliposomes prepared on the graphene grid (Scale bar = 10nm). b, Cryo-EM micrograph of empty liposomes prepared on the Quantifoil Au grid (Scale bar = 10nm). c, Analyses of the radii of the PIEZO1-residing side and the opposite pole of the 2D averaged proteoliposome vesicles of varied sizes. The inner and outer bilayers are approximated with the red and yellow dashed circles that are based on the PIEZO1-residing pole and the opposite pole of the same vesicle, respectively.

Extended Data Fig. 3 Structural determination and analyses of the curved PIEZO1 structure derived from proteoliposomes.

a, 2D class averages of PIEZO1 proteoliposomes with a circular mask of 25 nm diameter, showing the cap domain located inside the vesicles. On the basis of the abruptly changed curvature, the red arrows might indicate the boundary between the PIEZO1-residing side and the opposite side lacking proteins. b, Local resolution maps of the curved PIEZO1 structure viewed from the top, side and bottom. c, Gold-standard Fourier shell correlation (FSC) curve of the indicated density map. The reported resolution was based on the FSC = 0.143 criteria. d, Side view of the 3D density map of the water-drop-shaped proteoliposome showing the resolved lipid bilayer and the embedded PIEZO1 at the indicated contour level. e, Cryo-EM map of the curved PIEZO1 structure derived from proteoliposomes at the contour level of 4 and 6. Compared to the density map resolved in detergent micelles (EMD: 6865) (f), the PIEZO1 map derived from proteoliposomes contains extra patches of densities in-between the blades and in parallel to the inner membrane layer. These densities are noticeable even at a high contour level of 4 and consist of the modeled α1-helix of the clasp domain (Claspα1), the α-helix preceding TM33 (TM33pre-α1), and potentially unmodeled intracellular loop regions that are stabilized by interacting with lipid layers. This layer of membrane-parallel structure might help to stabilize the bowl-shaped structure of PIEZO1 in lipid membranes. f, Cryo-EM map of the PIEZO1 structure derived from detergent micelles (EMD 6865) at the contour level of 6. g, The cartoon model of the curved PIEZO1 structure derived from proteoliposomes. The featured structural domains are labeled. The resolved blade lipids and pore lipids are shown in blue and green, respectively. h, Pore radius along the central axis of the ion conduction pathway of the indicated PIEZO1 structures derived from either detergent micelles (5Z10 and 6B3R) or the curved structure derived from proteoliposomes. The residues forming the TM gate and intracellular constriction neck are labeled. i, Surface presentation of the curved PIEZO1 structure colored based on lipophilicity, from gold (lipophilic) to blue (hydrophilic) and surface presentation of the blade lipids and the pore lipid enclosed in the dashed box, which is enlarged in the right box either in surface presentation or in cartoon model. The lateral portal is indicated by the red dashed box.

Extended Data Fig. 4 Flowchart of EM data processing of the proteoliposomes with PIEZO1 being reconstituted in the outside-in configuration.

Details of data processing were described in the Imaging processing part of Methods.

Extended Data Fig. 5 Local EM density of the indicated domains of the curved PIEZO1 structure derived from proteoliposomes.

a, The helices are shown in cartoon representation with side chains as sticks. The cryo-EM density is shown as gray mesh. b, A side view of the curved PIEZO1 structure showing the blade lipid densities at the boundary of neighboring THU6 to THU9. c and d, A side view of the OH-IH enclosed central pore module showing the pore lipid densities either in the curved (c) or the flattened state (d).

Extended Data Fig. 6 Structural determination and analyses of the flattened PIEZO1 structure derived from proteoliposomes.

a, 2D class averages of the D-shaped PIEZO1 proteoliposome vesicles with a circular mask of 28 nm diameter. b, Gold-standard Fourier shell correlation (FSC) curve of the flattened PIEZO1 structure. The reported resolution was based on the FSC = 0.143 criteria. c, Local resolution maps of the flattened PIEZO1 structure viewed from the top, side and bottom. d, The alphaFold2 predicted PIEZO1 structure with the wedge domain shown in orange. e, The indicated views of the cartoon model of the flattened PIEZO1 structure. The featured domains are labeled. f, A bottom view of the overlaid curved and flattened cryo-EM maps showing the difference of the central plug density. g, A transparent view of the cryo-EM density of the lateral plug and latch domain showing the density variation of the lateral plug between 3D classified structures. h, Hydrophobic surface presentation of the flattened PIEZO1 structure and surface presentation of the pore lipid enclosed in the dashed box, which is enlarged in the right box either in the hydrophobic surface presentation or in cartoon model.

Extended Data Fig. 7 Flowchart of EM data processing of the proteoliposomes with PIEZO1 being reconstituted in the outside-out configuration.

Details of data processing were described in the Imaging processing part of Methods.

Extended Data Fig. 8 Structural comparisons.

a, Top view of the superimposed PIEZO1 structures as indicated. For clarity, the extracellular cap and loops are omitted. The displacement of the THU4 is labeled. b, Top view of the superimposed central pore region of the curved and flattened PIEZO1 structures (salmon red and cyan, respectively). The wedge domain of the flattened structure is shown in orange. c, Top view of the superimposed cap of the curved and flattened PIEZO1 structures (salmon red and cyan, respectively) and the PIEZO2 structure (PDB: 6KG7) (gray). The displacement of the Capα1-helix domain is labeled. d, A bottom view of the superimposed central pore of the curved and flattened structures of PIEZO1 showing the unchanged residues that form the intracellular constriction neck.

Extended Data Table 1 Cryo-EM data collection, refinement and validation statistics

Supplementary information

Reporting Summary

Peer Review File

Supplementary Video 1

Expansion of the PIEZO1 channel. Top view of the structural rearrangement from the curved to the flattened state of PIEZO1.

Supplementary Video 2

Flattening of the PIEZO1 channel. Side view of the structural rearrangement from the curved to the flattened state of PIEZO1.

Supplementary Video 3

Gating of the PIEZO1 channel. Top view of the central pore dilation from the curved to the flattened state of PIEZO1.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, X., Lin, C., Chen, X. et al. Structure deformation and curvature sensing of PIEZO1 in lipid membranes. Nature 604, 377–383 (2022). https://doi.org/10.1038/s41586-022-04574-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41586-022-04574-8

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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