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3D Artificial Cell Membranes as Versatile Platforms for Biological Applications

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Abstract

Artificial cell membranes, emulating biological membranes, have been used to elucidate the physiological functions of cells and realize biological applications. Advanced methodologies, along with considerations of biological/functional aspects, have enabled the development of various forms/types of artificial cell membranes commonly based on a lipid bilayer. Previous review articles have extensively explored 2-dimensional membranes but lack consideration on 3-dimensional membranes, which exhibit many advantages for biological platforms, such as large surface area, high stability, and ease of observation. Indeed, 3-dimensional membranes can accommodate a higher population of membrane proteins and show a more sensitive response to analytes than planar membranes. This review highlights the developments of artificial cell membranes in terms of structures and fabrication strategies, with a focus on 3-dimensional free-standing lipid membranes, and concludes with remarks on current key issues and challenges to evolve artificial cell membranes to another level.

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Fig. 1

Copyright 2006, Cell Press. d Schematic drawing of a BLM produced on a microaperture of a silicon chip, in which the aperture was tapered and treated with a silane coupling agent. Reprinted with permission from [43]. Copyright 2018, American Chemical Society. e Illustration of a droplet interface bilayer (DIB). f Solvent-free BLM formed by bursting giant unilamellar vesicles (GUVs) on a microfabricated aperture. g Schematics of formation steps of BLM arrays in a microfluidic channel (left) and the resulting BLM arrays encapsulating green fluorescence dye, Alexa 488, formed on microchambers with 4 μm in diameter (right). Reprinted with permission from [58]. Copyright 2014, Nature Publishing Group

Fig. 2

Copyright 2003, American Chemical Society. b Schematic diagram of receptor-ligand pair based immobilization mechanism of a single vesicle to a substrate (left), where biotin ligands on the vesicle strongly bind to streptavidin patterned on the substrate, and fluorescence images of high-density arrays (every 800 nm, ~ 106 mm−2) of single vesicles labeled with rhodamine (red) and oregon488 (green) (right). Reproduced with permission from [71]. Copyright 2003, Wiley. c Schematic drawing of a microfluidic platform for vesicle formation, trapping, and drug testing, with fluorescence images of produced vesicles for A and trapped vesicles for B in the inset. Reproduced with permission from [73]. Copyright 2019, The Royal Society of Chemistry

Fig. 3

Copyright 2011, IEEE. b Illustration of hydrogel stamping of lipids/proteins on ITO substrate and electroformation of giant proteoliposomes from lipid/protein films (left) and corresponding fluorescence images of the lipid/protein films and the proteoliposomes produced by electroformation (right). Reproduced with permission from [34]. Copyright 2013, Wiley. c Schemes of formation of GUVs on a homogeneous hydrogel film (top left) and on a micropatterned hydrogel film (top right), and fluorescence image of an array of GUVs formed on a micropatterned hydrogel with the highly magnified image in the inset (bottom). Reproduced with permission from [77]. Copyright 2019, American Chemical Society

Fig. 4

Copyright 2019, Wiley. b Geometry (left) and net charge distribution (right) of 3DFLBs: i) at low frequencies, 3DFLBs are squeezed by the radial Maxwell stress (TMW) or pressure (PMW) arising from the tangential electric field, hence 3DFLBs adopt a prolate shape, ii) and iii) at intermediate frequencies, due to the difference in the conductivity conditions, the net charges across the membrane, illustrated with pluses and minuses, differ depending on the values of the conductivity inside (λin) and outside (λout) of the membrane. The forces applied to the charges by the normal and the tangential electric fields deforms 3DFLBs into a prolate for λin > λex ii) and an oblate for λin < λex iii), and iv) at high frequencies, the electric charges cannot follow the oscillations of the electric field, leading to relax the shape of 3DFLBs into spherical. The green arrows indicate the change of cylindrical lipid structure caused by the morphology changes of semispherical lipid structures owing to energy minimization in lipid membrane surface. c Cross-sectional confocal fluorescence images of 3DFLBs in various shapes generated with different frequencies (left) and comparison of fluorescence intensities of unilamellar and multilamellar 3DFLBs to confirm the relation between lamellarity and sealing property (right) with the corresponding fluorescence images of 3DFLBs in sealing and leaky modes in the inset. Reproduced with permission from [36]. Copyright 2018, American Chemical Society

Fig. 5

Copyright 2019, Elsevier

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Acknowledgements

This work was supported by the Korean Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health and Welfare, the Ministry of Food and Drug Safety) (9991006807, KMDF_PR_20200901_0134_2021_01), supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (NRF-2020R1A2C2100363), and also supported by KIST Institutional Program (2E31502).

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  1. Won Bae Han, Dong-Hyun Kang contributed equally to this work.

Authors and Affiliations

  1. Creative Research Center for Brain Science, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea

    Won Bae Han, Dong-Hyun Kang & Tae Song Kim

  2. KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea

    Won Bae Han

  3. Micro Nano Fab Center, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea

    Dong-Hyun Kang

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Han, W.B., Kang, DH. & Kim, T.S. 3D Artificial Cell Membranes as Versatile Platforms for Biological Applications. BioChip J 16, 215–226 (2022). https://doi.org/10.1007/s13206-022-00066-z

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