Skip to main content

Thank you for visiting 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.

Transmembrane transport in inorganic colloidal cell-mimics


A key aspect of living cells is their ability to harvest energy from the environment and use it to pump specific atomic and molecular species in and out of their system—typically against an unfavourable concentration gradient1. Active transport allows cells to store metabolic energy, extract waste and supply organelles with basic building blocks at the submicrometre scale. Unlike living cells, abiotic systems do not have the delicate biochemical machinery that can be specifically activated to precisely control biological matter2,3,4,5. Here we report the creation of microcapsules that can be brought out of equilibrium by simple global variables (illumination and pH), to capture, concentrate, store and deliver generic microscopic payloads. Borrowing no materials from biology, our design uses hollow colloids serving as spherical cell-membrane mimics, with a well-defined single micropore. Precisely tunable monodisperse capsules are the result of a synthetic self-inflation mechanism and can be produced in bulk quantities. Inside the hollow unit, a photoswitchable catalyst6 produces a chemical gradient that propagates to the exterior through the membrane’s micropore and pumps target objects into the cell, acting as a phoretic tractor beam7. An entropic energy barrier8,9 brought about by the micropore’s geometry retains the cargo even when the catalyst is switched off. Delivery is accomplished on demand by reversing the sign of the phoretic interaction. Our findings provide a blueprint for developing the next generation of smart materials, autonomous micromachinery and artificial cell-mimics.

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

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Self-inflating droplets.
Fig. 2: Tunable mechanical properties.
Fig. 3: Micropore fabrication.
Fig. 4: Active transport.

Data availability

The data that support the findings of this study are available from the corresponding authors on request.


  1. Skou, J. C. & Esmann, M. The Na,K-ATPase. J. Bioenerg. Biomembr. 24, 249–261 (1992).

    CAS  PubMed  Google Scholar 

  2. Shang, L. & Zhao, Y. Droplet-templated synthetic cells. Matter 4, 95–115 (2021).

    Article  CAS  Google Scholar 

  3. Rodríguez-Arco, L., Li, M. & Mann, S. Phagocytosis-inspired behaviour in synthetic protocell communities of compartmentalized colloidal objects. Nat. Mater. 16, 857–863 (2017).

    Article  ADS  Google Scholar 

  4. Rideau, E., Dimova, R., Schwille, P., Wurm, F. R. & Landfester, K. Liposomes and polymersomes: a comparative review towards cell mimicking. Chem. Soc. Rev. 47, 8572–8610 (2018).

    Article  CAS  Google Scholar 

  5. Dinsmore, A. D. et al. Colloidosomes: selectively permeable capsules composed of colloidal particles. Science 298, 1006–1009 (2002).

    Article  CAS  ADS  Google Scholar 

  6. Sugimoto, T., Khan, M. M. & Muramatsu, A. Preparation of monodisperse peanut-type α-Fe2O3 particles from condensed ferric hydroxide gel. Colloids Surf. A 70, 167–169 (1993).

    Article  CAS  Google Scholar 

  7. Palacci, J. et al. Light-activated self-propelled colloids. Philos. Trans. R. Soc. A 372, 20130372 (2014).

    Article  ADS  Google Scholar 

  8. Cheng, K. L., Sheng, Y. J. & Tsao, H. K. Brownian escape and force-driven transport through entropic barriers: particle size effect. J. Chem. Phys. 129, 184901 (2008).

    Article  ADS  Google Scholar 

  9. Grigoriev, I. V., Makhnovskii, Y. A., Berezhkovskii, A. M. & Zitserman, V. Y. Kinetics of escape through a small hole. J. Chem. Phys. 116, 9574–9577 (2002).

    Article  CAS  ADS  Google Scholar 

  10. Wadhams, G. H. & Armitage, J. P. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol. 5, 1024–1037 (2004).

    Article  CAS  Google Scholar 

  11. Tweedy, L. et al. Seeing around corners: cells solve mazes and respond at a distance using attractant breakdown. Science 369, eaay9792 (2020).

    Article  CAS  Google Scholar 

  12. Taylor, J. W., Eghtesadi, S. A., Points, L. J., Liu, T. & Cronin, L. Autonomous model protocell division driven by molecular replication. Nat. Commun. 8, 237 (2017).

    Article  CAS  ADS  Google Scholar 

  13. Zhu, T. F., Adamala, K., Zhang, N. & Szostak, J. W. Photochemically driven redox chemistry induces protocell membrane pearling and division. Proc. Natl Acad. Sci. USA 109, 9828–9832 (2012).

    Article  CAS  ADS  Google Scholar 

  14. Zhu, T. F. & Szostak, J. W. Coupled growth and division of model protocell membranes. J. Am. Chem. Soc. 131, 5705–5713 (2009).

    Article  CAS  Google Scholar 

  15. Yewdall, N. A., Mason, A. F. & van Hest, J. C. M. The hallmarks of living systems: towards creating artificial cells. Interface Focus 8, 20180023 (2018).

    Article  Google Scholar 

  16. Yang, Z., Wei, J., Sobolev, Y. I. & Grzybowski, B. A. Systems of mechanized and reactive droplets powered by multi-responsive surfactants. Nature 553, 313–318 (2018).

    Article  CAS  ADS  Google Scholar 

  17. Qiao, Y., Li, M., Booth, R. & Mann, S. Predatory behaviour in synthetic protocell communities. Nat. Chem. 9, 110–119 (2017).

    Article  CAS  Google Scholar 

  18. Yin, Y. et al. Non-equilibrium behaviour in coacervate-based protocells under electric-field-induced excitation. Nat. Commun. 7, 10658 (2016).

    Article  CAS  ADS  Google Scholar 

  19. Fujii, S., Matsuura, T., Sunami, T., Kazuta, Y. & Yomo, T. In vitro evolution of α-hemolysin using a liposome display. Proc. Natl Acad. Sci. USA 110, 16796–16801 (2013).

    Article  CAS  ADS  Google Scholar 

  20. Li, G., Wang, L., Ni, H. & Pittman, C. U. Polyhedral oligomeric silsesquioxane (POSS) polymers and copolymers: a review. J. Inorg. Organomet. Polym. Mater. 11, 123–154 (2001).

    Article  CAS  Google Scholar 

  21. van der Wel, C. et al. Preparation of colloidal organosilica spheres through spontaneous emulsification. Langmuir 33, 8174–8180 (2017).

    Article  Google Scholar 

  22. Okubo, M., Kobayashi, H., Huang, C., Miyanaga, E. & Suzuki, T. Water absorption behavior of polystyrene particles prepared by emulsion polymerization with nonionic emulsifiers and innovative easy synthesis of hollow particles. Langmuir 33, 3468–3475 (2017).

    Article  CAS  Google Scholar 

  23. Shi, H., Huang, C., Liu, X. & Okubo, M. Role of osmotic pressure for the formation of sub-micrometer-sized, hollow polystyrene particles by heat treatment in aqueous dispersed systems. Langmuir 35, 12150–12157 (2019).

    Article  CAS  Google Scholar 

  24. Kim, S. H., Park, J. G., Choi, T. M., Manoharan, V. N. & Weitz, D. A. Osmotic-pressure-controlled concentration of colloidal particles in thin-shelled capsules. Nat. Commun. 5, 3068 (2014).

    Article  ADS  Google Scholar 

  25. Silletta, E. V., Xu, Z., Youssef, M., Sacanna, S. & Jerschow, A. Monitoring molecular transport across colloidal membranes. J. Phys. Chem. B 122, 4931–4936 (2018).

    Article  CAS  Google Scholar 

  26. Datta, S. S. et al. Delayed buckling and guided folding of inhomogeneous capsules. Phys. Rev. Lett. 109, 134302 (2012).

    Article  ADS  Google Scholar 

  27. Opdam, J., Tuinier, R., Hueckel, T., Snoeren, T. J. & Sacanna, S. Selective colloidal bonds via polymer-mediated interactions. Soft Matter 16, 7438–7446 (2020).

    Article  CAS  ADS  Google Scholar 

  28. Kim, S. H., Shim, J. W., Lim, J. M., Lee, S. Y. & Yang, S. M. Microfluidic fabrication of microparticles with structural complexity using photocurable emulsion droplets. New J. Phys. 11, 075014 (2009).

    Article  ADS  Google Scholar 

  29. Hyuk Im, S., Jeong, U. & Xia, Y. Polymer hollow particles with controllable holes in their surfaces. Nat. Mater. 4, 671–675 (2005).

    Article  CAS  ADS  Google Scholar 

  30. Qiu, J. et al. Encapsulation of a phase-change material in nanocapsules with a well-defined hole in the wall for the controlled release of drugs. Angew. Chem. Int. Edn Engl. 58, 10606–10611 (2019).

    Article  CAS  Google Scholar 

  31. Sacanna, S. et al. Shaping colloids for self-assembly. Nat. Commun. 4, 1688 (2013).

    Article  ADS  Google Scholar 

  32. Kar, A., Chiang, T. Y., Ortiz Rivera, I., Sen, A. & Velegol, D. Enhanced transport into and out of dead-end pores. ACS Nano 9, 746–753 (2015).

    Article  CAS  Google Scholar 

  33. Kuijk, A., van Blaaderen, A. & Imhof, A. Synthesis of monodisperse, rodlike silica colloids with tunable aspect ratio. J. Am. Chem. Soc. 133, 2346–2349 (2011).

    Article  CAS  Google Scholar 

Download references


This research was primarily supported by the US Army Research Office under award number W911NF2010117. S.S. acknowledges additional support from Kairos Ventures. W.T.M.I. acknowledges additional support from the Packard Foundation and the Brown Science Foundation.We thank T. Islam, M. Youssef, R. Bahn and M. Weigl for exploratory synthetic work, and L. Mahal for providing the E. coli sample.

Author information

Authors and Affiliations



Z.X. designed the cell-mimic synthetic protocol, synthesized all the colloidal systems and performed the active transport experiments. T.H. discovered the self-inflation mechanism and performed the preliminary synthetic work. S.S. conceived the study. S.S. and W.T.M.I. supervised and directed research. All authors analysed data, discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to William T. M. Irvine or Stefano Sacanna.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature thanks Yuanjin Zhao and the other, anonymous, reviewer(s) 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.

Extended data figures and tables

Extended Data Fig. 1 Functional emulsions.

a, Silsesquioxanes-based emulsions form via hydrolytic condensation of functionalized trialkoxysilane molecules (oil precursor). b, Monodispersed droplets nucleate upon the addition of ammonia and grow over time until the precursor is fully consumed. The cross-linking density of the newly formed oil-phase increases with the emulsion age τ, which is defined as the time passed from the addition of ammonia to the sample (nucleation). Ageing manifests with an increase of the oil-air contact angle formed by oil droplets resting on a clean silicon substrate (SEM images, right). c, The droplets can be fully cured by UV polymerization, resulting in a suspension of solid microspheres. Scale bars, 1 μm.

Extended Data Fig. 2 Self-inflation process.

a, b, Chemically induced osmotic pressure Πi transforms primed emulsion droplets (a) into expanding vesicles (b). The osmotic pressure is generated by charged monomers produced by the reaction between NaOH and the TPM oil phase. c, Expanding vesicles can be fixed via UV polymerization, resulting in solid capsules. Scale bars, 2 μm.

Extended Data Fig. 3 Full synthetic roadmap to self-inflating microcapsules.

a, b, The schematic shows an overview of the microcapsule fabrication process and highlights key steps. NaOH can be added to the emulsion droplets at any time τ during their ageing process (b). The droplets’ response, however, depends on both τ and the NaOH concentration, as shown in Fig. 1c. Panels a and b are described in detail in Extended Data Figs. 1 and 2, respectively.

Extended Data Fig. 4 Buckling behaviour.

ac, SEM images showing the three characteristic responses that we observed during the osmotic stress experiments in Fig. 2e. In Fig. 2, we refer to these responses as (a) intact, (b) mode 2 and (c) mode 1. We studied 11 different capsule geometries each tested against 9 different osmotic pressures. Within each sample, >90% of the capsules responded in the same manner. Scale bars, 2 μm.

Extended Data Fig. 5 Tunable micropores.

SEM images of cell-mimics displaying micropores in a wide range of sizes. Scale bar, 2 μm.

Extended Data Fig. 6 Growth and ageing of TPM droplets.

We characterize the emulsions by measuring the diameter of the droplets and the oil–air contact angle θ of the droplets on a silicon substrate. The graph shows a typical emulsion behaviour where θ increases monotonically with the droplet age τ, while their diameter reaches a maximum within 1 h from nucleation. Error bars, ±1 s.d.

Extended Data Fig. 7 Quantitative model of self-inflation.

The extent of the inflation for a forming vesicle can be predicted by balancing osmotic pressure and surface tension (solid line). The model is built assuming that the vesicle have a constant volume of oil and a fixed number of molecular species inside contributing to Πi. The experimental points are measurements of the vesicles size at different external osmotic pressures Πe. Radii are measured by SEM after polymerization and corrected for the relative density change (7% increase after polymerization21). Πe is adjusted using NaCl. R0, radius of the oil droplets measured before inflation. Error bars, ±1 s.d. Scale bars, 3 μm.

Extended Data Fig. 8 Ingestion of nanoparticles.

Optical microscopy time-lapse showing cell-mimics ingesting 450 nm (a) and 300 nm (b) PS tracers. In both experiments, the cell-mimic has a micropore of 1.1 μm. Scale bars are 1 μm.

Supplementary information


SI Video 1: Self-inflation of emulsion droplets. Video microscopy illustrating the self-inflation process. TPM emulsion droplets transform into vesicles upon exposure to NaOH


SI Video 2: Ingestion of PS spheres. Video microscopy showing cell mimics ingesting, holding and expelling PS tracers. (The video has been sped up by ~2 times)

SI Video 3: Ingestion of E.coli. Video microscopy showing cell mimics ingesting E.coli. (The video has been sped up by ~2 times)

SI Video 4: Ingestion of silica rods. Video microscopy showing cell mimics ingesting silica rods. (The video has been sped up by ~2 times)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xu, Z., Hueckel, T., Irvine, W.T.M. et al. Transmembrane transport in inorganic colloidal cell-mimics. Nature 597, 220–224 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


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.


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