Abstract
Recent years have seen substantial efforts aimed at constructing artificial cells from various molecular components with the aim of mimicking the processes, behaviours and architectures found in biological systems. Artificial cell development ultimately aims to produce model constructs that progress our understanding of biology, as well as forming the basis for functional bio-inspired devices that can be used in fields such as therapeutic delivery, biosensing, cell therapy and bioremediation. Typically, artificial cells rely on a bilayer membrane chassis and have fluid aqueous interiors to mimic biological cells. However, a desire to more accurately replicate the gel-like properties of intracellular and extracellular biological environments has driven increasing efforts to build cell mimics based on hydrogels. This has enabled researchers to exploit some of the unique functional properties of hydrogels that have seen them deployed in fields such as tissue engineering, biomaterials and drug delivery. In this Review, we explore how hydrogels can be leveraged in the context of artificial cell development. We also discuss how hydrogels can potentially be incorporated within the next generation of artificial cells to engineer improved biological mimics and functional microsystems.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cho, E. & Lu, Y. Compartmentalizing cell-free systems: toward creating life-like artificial cells and beyond. ACS Synth. Biol. 9, 2881–2901 (2020).
Zhu, Y., Guo, X., Liu, J., Li, F. & Yang, D. Emerging advances of cell-free systems toward artificial cells. Small Methods 4, 2000406 (2020).
Ayoubi-Joshaghani, M. H. et al. Cell-free protein synthesis: the transition from batch reactions to minimal cells and microfluidic devices. Biotechnol. Bioeng. 117, 1204–1229 (2020).
Boyd, M. A. & Kamat, N. P. Designing artificial cells towards a new generation of biosensors. Trends Biotechnol. 39, 927–939 (2021).
Laohakunakorn, N. et al. Bottom-up construction of complex biomolecular systems with cell-free synthetic biology. Front. Bioeng. Biotechnol. 8, 213 (2020).
Robinson, A. O., Venero, O. M. & Adamala, K. P. Toward synthetic life: biomimetic synthetic cell communication. Curr. Opin. Chem. Biol. 64, 165–173 (2021).
Xu, C., Hu, S. & Chen, X. Artificial cells: from basic science to applications. Mater. Today 19, 516–532 (2016).
Blain, J. C. & Szostak, J. W. Progress toward synthetic cells. Annu. Rev. Biochem. 83, 615–640 (2014).
Noireaux, V., Maeda, Y. T. & Libchaber, A. Development of an artificial cell, from self-organization to computation and self-reproduction. Proc. Natl Acad. Sci. USA 108, 3473–3480 (2011).
Salehi-Reyhani, A., Ces, O. & Elani, Y. Artificial cell mimics as simplified models for the study of cell biology. Exp. Biol. Med. 242, 1309–1317 (2017).
Krinsky, N. et al. Synthetic cells synthesize therapeutic proteins inside tumors. Adv. Healthc. Mater. 7, e1701163 (2018).
Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367–379 (2010).
Glass, J. I., Merryman, C., Wise, K. S., Hutchison, C. A. & Smith, H. O. Minimal cells-real and imagined. Cold Spring Harb. Perspect. Biol. 9, a023861 (2017).
Hutchison, C. A. et al. Design and synthesis of a minimal bacterial genome. Science 351, aad6253 (2016).
Göpfrich, K., Platzman, I. & Spatz, J. P. Mastering complexity: towards bottom-up construction of multifunctional eukaryotic synthetic cells. Trends Biotechnol. 36, 938–951 (2018).
Buddingh’, B. C. & Van Hest, J. C. M. Artificial cells: synthetic compartments with life-like functionality and adaptivity. Acc. Chem. Res. 50, 769–777 (2017).
Amy Yewdall, N., Mason, A. F. & Van Hest, J. C. M. The hallmarks of living systems: towards creating artificial cells. Interface Focus 8, 20180023 (2018).
Elani, Y., Law, R. V. & Ces, O. Vesicle-based artificial cells as chemical microreactors with spatially segregated reaction pathways. Nat. Commun. 5, 5305 (2014).
Kurokawa, C. et al. DNA cytoskeleton for stabilizing artificial cells. Proc. Natl Acad. Sci. USA 114, 7228–7233 (2017).
Deshpande, S., Wunnava, S., Hueting, D. & Dekker, C. Membrane tension–mediated growth of liposomes. Small 15, 1902898 (2019).
Zhang, S. et al. Engineering motile aqueous phase-separated droplets via liposome stabilisation. Nat. Commun. 12, 1673 (2021).
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).
Garamella, J., Majumder, S., Liu, A. P. & Noireaux, V. An adaptive synthetic cell based on mechanosensing, biosensing, and inducible gene circuits. ACS Synth. Biol. 8, 1913–1920 (2019).
Hindley, J. W. et al. Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells. Proc. Natl Acad. Sci. USA 116, 16711–16716 (2019).
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).
Li, M., Huang, X., Tang, T. Y. D. & Mann, S. Synthetic cellularity based on non-lipid micro-compartments and protocell models. Curr. Opin. Chem. Biol. 22, 1–11 (2014).
Huang, X. et al. Interfacial assembly of protein-polymer nano-conjugates into stimulus-responsive biomimetic protocells. Nat. Commun. 4, 2239 (2013).
Trevors, J. T. & Pollack, G. H. Hypothesis: the origin of life in a hydrogel environment. Prog. Biophys. Mol. Biol. 89, 1–8 (2005).
Moeendarbary, E. et al. The cytoplasm of living cells behaves as a poroelastic material. Nat. Mater. 12, 253–261 (2013).
Tibbitt, M. W. & Anseth, K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103, 655–663 (2009).
Peppas, N. A., Hilt, J. Z., Khademhosseini, A. & Langer, R. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006).
Zhang, Y. S. & Khademhosseini, A. Advances in engineering hydrogels. Science 356, eaaf3267 (2017).
Gawade, P. M., Shadish, J. A., Badeau, B. A. & DeForest, C. A. Logic-based delivery of site-specifically modified proteins from environmentally responsive hydrogel biomaterials. Adv. Mater. 31, 1902462 (2019).
Fares, M. M. et al. Interpenetrating network gelatin methacryloyl (GelMA) and pectin-g-PCL hydrogels with tunable properties for tissue engineering. Biomater. Sci. 6, 2938–2950 (2018).
Lou, J., Stowers, R., Nam, S., Xia, Y. & Chaudhuri, O. Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture. Biomaterials 154, 213–222 (2018).
Liao, M. et al. Wearable, healable, and adhesive epidermal sensors assembled from mussel-inspired conductive hybrid hydrogel framework. Adv. Funct. Mater. 27, 1703852 (2017).
Gil, M. S., Thambi, T., Phan, V. H. G., Kim, S. H. & Lee, D. S. Injectable hydrogel-incorporated cancer cell-specific cisplatin releasing nanogels for targeted drug delivery. J. Mater. Chem. B 5, 7140–7152 (2017).
Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).
Knipe, J. M., Strong, L. E. & Peppas, N. A. Enzyme- and pH-responsive microencapsulated nanogels for oral delivery of siRNA to induce TNF-α knockdown in the intestine. Biomacromolecules 17, 788–797 (2016).
Ahmed, E. M. Hydrogel: preparation, characterization, and applications: a review. J. Adv. Res. 6, 105–121 (2015).
Gun’ko, V. M., Savina, I. N. & Mikhalovsky, S. V. Properties of water bound in hydrogels. Gels 3, 37 (2017).
Zhu, J. & Marchant, R. E. Design properties of hydrogel tissue-engineering scaffolds. Expert. Rev. Med. Device 8, 607–626 (2011).
Du, X., Zhou, J., Shi, J. & Xu, B. Supramolecular hydrogelators and hydrogels: from soft matter to molecular biomaterials. Chem. Rev. 115, 13165–13307 (2015).
Janeček, E.-R. et al. Hybrid supramolecular and colloidal hydrogels that bridge multiple length scales. Angew. Chem. Int. Ed. 54, 5383–5388 (2015).
Laftah, W. A., Hashim, S. & Ibrahim, A. N. Polymer hydrogels: a review. Polym. Plast. Technol. Eng. 50, 1475–1486 (2011).
Shalviri, A., Liu, Q., Abdekhodaie, M. J. & Wu, X. Y. Novel modified starch-xanthan gum hydrogels for controlled drug delivery: synthesis and characterization. Carbohydr. Polym. 79, 898–907 (2010).
Xiong, X. et al. Responsive DNA-based hydrogels and their applications. Macromol. Rapid Commun. 34, 1271–1283 (2013).
Fabrini, G., Minard, A., Brady, R. A., Di Antonio, M. & Di Michele, L. Cation-responsive and photocleavable hydrogels from noncanonical amphiphilic DNA nanostructures. Nano Lett. 22, 602–611 (2022).
Nöll, T., Wenderhold-Reeb, S., Schönherr, H. & Nöll, G. Pristine DNA hydrogels from biotechnologically derived plasmid DNA. Angew. Chem. Int. Ed. 56, 12004–12008 (2017).
Hu, Y. et al. Bottom-up assembly of DNA–silica nanocomposites into micrometer-sized hollow spheres. Angew. Chem. Int. Ed. 58, 17269–17272 (2019).
Brady, R. A., Brooks, N. J., Cicuta, P. & Di Michele, L. Crystallization of amphiphilic DNA C-stars. Nano Lett. 17, 3276–3281 (2017).
Yue, K. et al. Visible light crosslinkable human hair keratin hydrogels. Bioeng. Transl. Med. 3, 37–48 (2018).
Catoira, M. C., Fusaro, L., Di Francesco, D., Ramella, M. & Boccafoschi, F. Overview of natural hydrogels for regenerative medicine applications. J. Mater. Sci. Mater. Med. 30, 115 (2019).
Van Vlierberghe, S., Dubruel, P. & Schacht, E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules 12, 1387–1408 (2011).
Rubio-Sanchez, R., Fabrini, G., Cicuta, P. & Di Michele, L. Amphiphilic DNA nanostructures for bottom-up synthetic biology. Chem. Commun. 57, 12725–12740 (2021).
Kahn, J. S., Hu, Y. & Willner, I. Stimuli-responsive DNA-based hydrogels: from basic principles to applications. Acc. Chem. Res. 50, 680–690 (2017).
Morya, V., Walia, S., Mandal, B. B., Ghoroi, C. & Bhatia, D. Functional DNA based hydrogels: development properties and biological applications. ACS Biomater. Sci. Eng. 6, 6021–6035 (2020).
English, M. A. et al. Programmable CRISPR-responsive smart materials. Science 365, 780–785 (2019).
Chen, G., Sato, T., Ushida, T., Ochiai, N. & Tateishi, T. Tissue engineering of cartilage using a hybrid scaffold of synthetic polymer and collagen.Tissue Eng. 10, 323–330 (2004).
Jian, H. et al. Dipeptide self-assembled hydrogels with tunable mechanical properties and degradability for 3D bioprinting. ACS Appl. Mater. Interfaces 11, 46419–46426 (2019).
Hennink, W. E. & van Nostrum, C. F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 64, 223–236 (2012).
Wade, R. J., Bassin, E. J., Rodell, C. B. & Burdick, J. A. Protease-degradable electrospun fibrous hydrogels. Nat. Commun. 6, 6639 (2015).
Crivello, J. V. & Reichmanis, E. Photopolymer materials and processes for advanced technologies. Chem. Mater. 26, 533–548 (2014).
Braun, D. Origins and development of initiation of free radical polymerization processes. Int. J. Polym. Sci. 2009, 893234 (2009).
Sarac, A. S. Redox polymerization. Prog. Polym. Sci. 24, 1149–1204 (1999).
Nimmo, C. M., Owen, S. C. & Shoichet, M. S. Diels-Alder click cross-linked hyaluronic acid hydrogels for tissue engineering. Biomacromolecules 12, 824–830 (2011).
Hiemstra, C., van der Aa, L. J., Zhong, Z., Dijkstra, P. J. & Feijen, J. Rapidly in situ-forming degradable hydrogels from dextram triols through Michael addition. Biomacromolecules 8, 1548–1556 (2007).
Javvaji, V., Baradwaj, A. G., Payne, G. F. & Raghavan, S. R. Light-activated ionic gelation of common biopolymers. Langmuir 27, 12591–12596 (2011).
Hu, W., Wang, Z., Xiao, Y., Zhang, S. & Wang, J. Advances in crosslinking strategies of biomedical hydrogels. Biomater. Sci. 7, 843–855 (2019).
Zhong, M. et al. Self-healable, tough and highly stretchable ionic nanocomposite physical hydrogels. Soft Matter 11, 4235–4241 (2015).
Koetting, M. C., Peters, J. T., Steichen, S. D. & Peppas, N. A. Stimulus-responsive hydrogels: theory, modern advances, and applications. Mater. Sci. Eng. R. Rep. 93, 1–49 (2015).
Chatterjee, S., Hui, P. C. L. & Kan, C. W. Thermoresponsive hydrogels and their biomedical applications: special insight into their applications in textile based transdermal therapy. Polymers 10, 480 (2018).
Drozdov, A. D. & Sommer-Larsen, P. Swelling of thermo-responsive gels under hydrostatic pressure. Meccanica 51, 1419–1434 (2016).
Gupta, P., Vermani, K. & Garg, S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug. Discov. Today 7, 569–579 (2002).
Xiang, T., Lu, T., Zhao, W. F. & Zhao, C. S. Ionic-strength responsive Zwitterionic copolymer hydrogels with tunable swelling and adsorption behaviors. Langmuir 35, 1146–1155 (2019).
Rosales, A. M., Vega, S. L., DelRio, F. W., Burdick, J. A. & Anseth, K. S. Hydrogels with reversible mechanics to probe dynamic cell microenvironments. Angew. Chem. Int. Ed. 56, 12132–12136 (2017).
Takashima, Y. et al. Expansion-contraction of photoresponsive artificial muscle regulated by host-guest interactions. Nat. Commun. 3, 1270 (2012).
Kim, S. J., Park, S. J., Kim, I. Y., Shin, M. S. & Kim, S. I. Electric stimuli responses to poly(vinyl alcohol)/chitosan interpenetrating polymer network hydrogel in NaCl solutions. J. Appl. Polym. Sci. 86, 2285–2289 (2002).
Wu, C. H. et al. Ultrasound-responsive NIPAM-based hydrogels with tunable profile of controlled release of large molecules. Ultrasonics 83, 157–163 (2018).
Emi, T. T. et al. Pulsatile chemotherapeutic delivery profiles using magnetically responsive hydrogels. ACS Biomater. Sci. Eng. 4, 2412–2423 (2018).
Orlov, Y., Xu, X. & Maurer, G. Equilibrium swelling of N-isopropyl acrylamide based ionic hydrogels in aqueous solutions of organic solvents: comparison of experiment with theory. Fluid Phase Equilib. 249, 6–16 (2006).
Matsuda, T., Kawakami, R., Namba, R., Nakajima, T. & Gong, J. P. Mechanoresponsive self-growing hydrogels inspired by muscle training. Science 363, 504–508 (2019).
Zhou, Y. & Jin, L. Hydrolysis-induced large swelling of polyacrylamide hydrogels. Soft Matter 16, 5740–5749 (2020).
Vemula, P. K., Cruikshank, G. A., Karp, J. M. & John, G. Self-assembled prodrugs: an enzymatically triggered drug-delivery platform. Biomaterials 30, 383–393 (2009).
Nakahata, M., Takashima, Y., Yamaguchi, H. & Harada, A. Redox-responsive self-healing materials formed from host-guest polymers. Nat. Commun. 2, 511 (2011).
Gaharwar, A. K., Peppas, N. A. & Khademhosseini, A. Nanocomposite hydrogels for biomedical applications. Biotechnol. Bioeng. 111, 441–453 (2014).
de Almeida, P. et al. Cytoskeletal stiffening in synthetic hydrogels. Nat. Commun. 10, 609 (2019).
Beebe, D. J. et al. Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature 404, 588–590 (2000).
Jiang, Z. et al. Strong, self‐healable, and recyclable visible‐light‐responsive hydrogel actuators. Angew. Chem. Int. Ed. 59, 7049–7056 (2020).
Guiseppi-Elie, A., Brahim, S. I. & Narinesingh, D. A chemically synthesized artificial pancreas: release of insulin from glucose-responsive hydrogels. Adv. Mater. 14, 743–746 (2002).
Fels, J., Orlov, S. N. & Grygorczyk, R. The hydrogel nature of mammalian cytoplasm contributes to osmosensing and extracellular pH sensing. Biophys. J. 96, 4276–4285 (2009).
Niederholtmeyer, H., Chaggan, C. & Devaraj, N. K. Communication and quorum sensing in non-living mimics of eukaryotic cells. Nat. Commun. 9, 5027 (2018).
Rosales, A. M. & Anseth, K. S. The design of reversible hydrogels to capture extracellular matrix dynamics. Nat. Rev. Mater. 1, 15012 (2016).
Peppas, N. A., Bures, P., Leobandung, W. & Ichikawa, H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50, 27–46 (2000).
Spitzer, J. J. & Poolman, B. Electrochemical structure of the crowded cytoplasm. Trends Biochem. Sci. 30, 536–541 (2005).
Aumailley, M. & Gayraud, B. Structure and biological activity of the extracellular matrix. J. Mol. Med. 76, 253–265 (1998).
Newport, J. W. & Forbes, D. J. The nucleus: structure, function, and dynamics. Annu. Rev. Biochem. 56, 535–565 (1987).
Rowat, A. C., Lammerding, J., Herrmann, H. & Aebi, U. Towards an integrated understanding of the structure and mechanics of the cell nucleus. BioEssays 30, 226–236 (2008).
Misteli, T. Physiological importance of RNA and protein mobility in the cell nucleus. Histochem. Cell Biol. 129, 5–11 (2008).
Ghosh, S., Chattoraj, S., Mondal, T. & Bhattacharyya, K. Dynamics in cytoplasm, nucleus, and lipid droplet of a live CHO cell: time-resolved confocal microscopy. Langmuir 29, 7975–7982 (2013).
Aufinger, L. & Simmel, F. C. Artificial gel-based organelles for spatial organization of cell-free gene expression reactions. Angew. Chem. Int. Ed. 57, 17245–17248 (2018).
Yue, B. Biology of the extracellular matrix: an overview. J. Glaucoma 23, S20–S23 (2014).
Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).
Giobbe, G. G. et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat. Commun. 10, 5658 (2019).
Cox, T. R. & Erler, J. T. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis. Model. Mech. 4, 165–178 (2011).
Benoit, D. S. W., Schwartz, M. P., Durney, A. R. & Anseth, K. S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat. Mater. 7, 816–823 (2008).
Khan, F., Tare, R. S., Oreffo, R. O. C. & Bradley, M. Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angew. Chem. Int. Ed. 48, 978–982 (2009).
Liu, H. et al. Advances in hydrogels in organoids and organs-on-a-chip. Adv. Mater. 31, 1902042 (2019).
Deller, R. C. et al. Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation. Nat. Commun. 10, 1887 (2019).
Fletcher, D. A. & Mullins, R. D. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010).
Hohmann, T. & Dehghani, F. The cytoskeleton — a complex interacting meshwork. Cells 8, 362 (2019).
Bashirzadeh, Y. & Liu, A. P. Encapsulation of the cytoskeleton: towards mimicking the mechanics of a cell. Soft Matter 15, 8425–8436 (2019).
Tank, D. W., Wu, E. S. & Webb, W. W. Enhanced molecular diffusibility in muscle membrane blebs: release of lateral constraints. J. Cell Biol. 92, 207–212 (1982).
Potma, E. O. et al. Reduced protein diffusion rate by cytoskeleton in vegetative and polarized Dictyostelium cells. Biophys. J. 81, 2010–2019 (2001).
Garamella, J., Regan, K., Aguirre, G., McGorty, R. J. & Robertson-Anderson, R. M. Anomalous and heterogeneous DNA transport in biomimetic cytoskeleton networks. Soft Matter 16, 6344–6353 (2020).
Sano, K. I. et al. Self-repairing filamentous actin hydrogel with hierarchical structure. Biomacromolecules 12, 4173–4177 (2011).
Litschel, T. et al. Reconstitution of contractile actomyosin rings in vesicles. Nat. Commun. 12, 2254 (2021).
Knoff, D. S., Szczublewski, H., Altamirano, D., Fajardo Cortes, K. A. & Kim, M. Cytoskeleton-inspired artificial protein design to enhance polymer network elasticity. Macromolecules 53, 3464–3471 (2020).
Luby-Phelps, K. The physical chemistry of cytoplasm and its influence on cell function: an update. Mol. Biol. Cell 24, 2593–2596 (2013).
Mastro, A. M., Babich, M. A., Taylor, W. D. & Keith, A. D. Diffusion of a small molecule in the cytoplasm of mammalian cells. Proc. Natl Acad. Sci. USA 81, 3414–3418 (1984).
Cameron, I. L. et al. Maintenance of ions, proteins and water in lens fiber cells before and after treatment with non-ionic detergents. Cell Biol. Int. 20, 127–137 (1996).
Elliott, G. F., Goodfellow, J. M. & Woolgar, A. E. Swelling studies of bovine corneal stroma without bounding membranes. J. Physiol. 298, 453–470 (1980).
Grygorczyk, R., Boudreault, F., Platonova, A. & Orlov, S. N. Salt and osmosensing: role of cytoplasmic hydrogel. Pflug. Arch. Eur. J. Physiol. 467, 475–487 (2015).
Toprakcioglu, Z., Challa, P. K., Morse, D. B. & Knowles, T. Attoliter protein nanogels from droplet nanofluidics for intracellular delivery. Sci. Adv. 6, eaay7952 (2020).
Tanaka, T. & Fillmore, D. J. Kinetics of swelling of gels. J. Chem. Phys. 70, 1214–1218 (1979).
Ahiabu, A. & Serpe, M. J. Rapidly responding pH- and temperature-responsive poly (N-isopropylacrylamide)-based microgels and assemblies. ACS Omega 2, 1769–1777 (2017).
Varga, I., Szalai, I., Mészaros, R. & Gilányi, T. Pulsating pH-responsive nanogels. J. Phys. Chem. B 110, 20297–20301 (2006).
Parisi, O. I. et al. Controlled release of sunitinib in targeted cancer therapy: smart magnetically responsive hydrogels as restricted access materials. RSC Adv. 5, 65308–65315 (2015).
Trantidou, T. et al. Engineering compartmentalized biomimetic micro- and nanocontainers. ACS Nano 11, 6549–6565 (2017).
Margolis, L. & Sadovsky, Y. The biology of extracellular vesicles: the known unknowns. PLoS Biol. 17, e3000363 (2019).
Milo, R. & Phillips, R. Cell Biology by the Numbers (Garland Science, 2015).
Sato, Y. & Takinoue, M. Capsule-like DNA hydrogels with patterns formed by lateral phase separation of DNA nanostructures. JACS Au 2, 159–168 (2022).
Saunders, B. R. & Vincent, B. Microgel particles as model colloids: theory, properties and applications. Adv. Colloid Interface Sci. 80, 1–25 (1999).
Downey, J. S., Frank, R. S., Li, W. H. & Stöver, H. D. H. Growth mechanism of poly(divinylbenzene) microspheres in precipitation polymerization. Macromolecules 32, 2838–2844 (1999).
Hu, X., Tong, Z. & Lyon, L. A. Multicompartment core/shell microgels. J. Am. Chem. Soc. 132, 11470–11472 (2010).
Städler, B. et al. Polymer hydrogel capsules: en route toward synthetic cellular systems. Nanoscale 1, 68–73 (2009).
Kasahara, Y., Sato, Y., Masukawa, M. K., Okuda, Y. & Takinoue, M. Photolithographic shape control of DNA hydrogels by photo-activated self-assembly of DNA nanostructures. APL Bioeng. 4, 016109 (2020).
Dendukuri, D., Pregibon, D. C., Collins, J., Hatton, T. A. & Doyle, P. S. Continuous-flow lithography for high-throughput microparticle synthesis. Nat. Mater. 5, 365–369 (2006).
Cangialosi, A. et al. DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling. Science 357, 1126–1130 (2017).
Chen, K. et al. Low modulus biomimetic microgel particles with high loading of hemoglobin. Biomacromolecules 13, 2748–2759 (2012).
Kilian, K. A., Bugarija, B., Lahn, B. T. & Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl Acad. Sci. USA 107, 4872–4877 (2010).
Muir, V. G., Qazi, T. H., Shan, J., Groll, J. & Burdick, J. A. Influence of microgel fabrication technique on granular hydrogel properties. ACS Biomater. Sci. Eng. 7, 4269–4281 (2021).
Lee, S., Che, B., Tai, M., Li, W. & Kim, S. H. Designing semipermeable hydrogel shells with controlled thickness through internal osmosis in triple-emulsion droplets. Adv. Funct. Mater. 31, 2105477 (2021).
Chen, M., Bolognesi, G. & Vladisavljević, G. T. Crosslinking strategies for the microfluidic production of microgels. Molecules 26, 3752 (2021).
Wan, J. Microfluidic-based synthesis of hydrogel particles for cell microencapsulation and cell-based drug delivery. Polymers 4, 1084–1108 (2012).
Utech, S. et al. Microfluidic generation of monodisperse, structurally homogeneous alginate microgels for cell encapsulation and 3D cell culture. Adv. Healthc. Mater. 4, 1628–1633 (2015).
Liao, Q. Q. et al. Biocompatible fabrication of cell-laden calcium alginate microbeads using microfluidic double flow-focusing device. Sens. Actuators A Phys. 279, 313–320 (2018).
Akbari, S. & Pirbodaghi, T. Microfluidic encapsulation of cells in alginate particles via an improved internal gelation approach. Microfluid. Nanofluid. 16, 773–777 (2014).
Huang, H. et al. Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture. Lab Chip 17, 1913–1932 (2017).
Zhao, Z. et al. Injectable microfluidic hydrogel microspheres for cell and drug delivery. Adv. Funct. Mater. 31, 2103339 (2021).
Chu, J. O. et al. Cell-inspired hydrogel microcapsules with a thin oil layer for enhanced retention of highly reactive antioxidants. ACS Appl. Mater. Interfaces 14, 2597–2604 (2022).
Choi, C. H. et al. One-step generation of cell-laden microgels using double emulsion drops with a sacrificial ultra-thin oil shell. Lab Chip 16, 1549–1555 (2016).
Baxani, D. K. et al. Bilayer networks within a hydrogel shell: a robust chassis for artificial cells and a platform for membrane studies. Angew. Chem. Int. Ed. 55, 14240–14245 (2016).
Thiele, J. et al. DNA-functionalized hydrogels for confined membrane-free in vitro transcription/translation. Lab Chip 14, 2651–2656 (2014).
He, F. et al. Controllable multicompartmental capsules with distinct cores and shells for synergistic release. ACS Appl. Mater. Interfaces 8, 8743–8754 (2016).
Xu, Y. et al. Liquid–liquid phase-separated systems from reversible gel–sol transition of protein microgels. Adv. Mater. 33, e2008670 (2021).
Martino, C., Lee, T. Y., Kim, S. H. & DeMello, A. J. Microfluidic generation of PEG-b-PLA polymersomes containing alginate-based core hydrogel. Biomicrofluidics 9, 024101 (2015).
Van Swaay, D. & Demello, A. Microfluidic methods for forming liposomes. Lab Chip 13, 752–767 (2013).
Trantidou, T., Friddin, M. S., Salehi-Reyhani, A., Ces, O. & Elani, Y. Droplet microfluidics for the construction of compartmentalised model membranes. Lab Chip 18, 2488–2509 (2018).
Ugrinic, M., DeMello, A. & Tang, T. Y. D. Microfluidic tools for bottom-up synthetic cellularity. Chem 5, 1727–1742 (2019).
Hong, J. S. et al. Microfluidic directed self-assembly of liposome-hydrogel hybrid nanoparticles. Langmuir 26, 11581–11588 (2010).
Peruzzi, J., Gutierrez, M. G., Mansfield, K. & Malmstadt, N. Dynamics of hydrogel-assisted giant unilamellar vesicle formation from unsaturated lipid systems. Langmuir 32, 12702–12709 (2016).
Weinberger, A. et al. Gel-assisted formation of giant unilamellar vesicles. Biophys. J. 105, 154–164 (2013).
Parigoris, E. et al. Facile generation of giant unilamellar vesicles using polyacrylamide gels. Sci. Rep. 10, 4824 (2020).
Huang, N., Guan, Y., Zhu, X. X. & Zhang, Y. Swelling kinetics of microgels embedded in a polyacrylamide hydrogel matrix. ChemPhysChem 15, 1785–1792 (2014).
Caliari, S. R. & Burdick, J. A. A practical guide to hydrogels for cell culture. Nat. Methods 13, 405–414 (2016).
Schmidt, S. et al. Adhesion and mechanical properties of PNIPAM microgel films and their potential use as switchable cell culture substrates. Adv. Funct. Mater. 20, 3235–3243 (2010).
Zhang, J. et al. Micropatterned soft hydrogels to study the interplay of receptors and forces in T cell activation. Acta Biomater. 119, 234–246 (2021).
Kamperman, T., Karperien, M., Le Gac, S. & Leijten, J. Single-cell microgels: technology, challenges, and applications. Trends Biotechnol. 36, 850–865 (2018).
Li, J., Wu, C., Chu, P. K. & Gelinsky, M. 3D printing of hydrogels: rational design strategies and emerging biomedical applications. Mater. Sci. Eng. R. Rep. 140, 100543 (2020).
Mulakkal, M. C., Trask, R. S., Ting, V. P. & Seddon, A. M. Responsive cellulose-hydrogel composite ink for 4D printing. Mater. Des. 160, 108–118 (2018).
Müller, J., Jäkel, A. C., Schwarz, D., Aufinger, L. & Simmel, F. C. Programming diffusion and localization of DNA signals in 3D-printed DNA-functionalized hydrogels. Small 16, 2001815 (2020).
Shiblee, M. N. I., Ahmed, K., Khosla, A., Kawakami, M. & Furukawa, H. 3D printing of shape memory hydrogels with tunable mechanical properties. Soft Matter 14, 7809–7817 (2018).
Sydney Gladman, A., Matsumoto, E. A., Nuzzo, R. G., Mahadevan, L. & Lewis, J. A. Biomimetic 4D printing. Nat. Mater. 15, 413–418 (2016).
Yang, C. et al. Hydrogel walkers with electro-driven motility for cargo transport. Sci. Rep. 5, 13622 (2015).
Xu, Z., Xu, Z. & Fu, J. Programmable and reversible 3D-/4D-shape-morphing hydrogels with precisely defined ion coordination. ACS Appl. Mater. Interfaces 12, 26476–26484 (2020).
Tan, H. et al. Heterogeneous multi-compartmental hydrogel particles as synthetic cells for incompatible tandem reactions. Nat. Commun. 8, 663 (2017).
Rollié, S., Mangold, M. & Sundmacher, K. Designing biological systems: systems engineering meets synthetic biology. Chem. Eng. Sci. 69, 1–29 (2012).
Hatori, M. N., Kim, S. C. & Abate, A. R. Particle-templated emulsification for microfluidics-free digital biology. Anal. Chem. 90, 9813–9820 (2018).
Fischlechner, M. et al. Evolution of enzyme catalysts caged in biomimetic gel-shell beads. Nat. Chem. 6, 791–796 (2014).
Jäckel, C. & Hilvert, D. Biocatalysts by evolution. Curr. Opin. Biotechnol. 21, 753–759 (2010).
Lin, W. et al. Cartilage-inspired, lipid-based boundary-lubricated hydrogels. Science 370, 335–338 (2020).
Bayley, H. et al. Droplet interface bilayers. Mol. Biosyst. 4, 1191–1208 (2008).
Elani, Y., Solvas, X. C. I., Edel, J. B., Law, R. V. & Ces, O. Microfluidic generation of encapsulated droplet interface bilayer networks (multisomes) and their use as cell-like reactors. Chem. Commun. 52, 5961–5964 (2016).
Strutt, R. et al. Activating mechanosensitive channels embedded in droplet interface bilayers using membrane asymmetry. Chem. Sci. 12, 2138–2145 (2021).
Funakoshi, K., Suzuki, H. & Takeuchi, S. Lipid bilayer formation by contacting monolayers in a microfluidic device for membrane protein analysis. Anal. Chem. 78, 8169–8174 (2006).
Allen-Benton, M., Findlay, H. E. & Booth, P. J. Probing membrane protein properties using droplet interface bilayers. Exp. Biol. Med. 244, 709–720 (2019).
Li, J. et al. Formation of polarized, functional artificial cells from compartmentalized droplet networks and nanomaterials, using one-step, dual-material 3D-printed microfluidics. Adv. Sci. 7, 1901719 (2020).
Bayoumi, M., Bayley, H., Maglia, G. & Sapra, K. T. Multi-compartment encapsulation of communicating droplets and droplet networks in hydrogel as a model for artificial cells. Sci. Rep. 7, 45167 (2017).
Downs, F. G. et al. Multi-responsive hydrogel structures from patterned droplet networks. Nat. Chem. 12, 363–371 (2020).
Hoskin, C. E. G., Schild, V. R., Vinals, J. & Bayley, H. Parallel transmission in a synthetic nerve. Nat. Chem. 14, 650–657 (2022).
Jensen, B. E. B. et al. Lipogels: surface-adherent composite hydrogels assembled from poly(vinyl alcohol) and liposomes. Nanoscale 5, 6758–6766 (2013).
Li, R. et al. Injectable and in situ-formable thiolated chitosan-coated liposomal hydrogels as curcumin carriers for prevention of in vivo breast cancer recurrence. ACS Appl. Mater. Interfaces 12, 17936–17948 (2020).
Cheng, R. et al. Mechanically enhanced lipo-hydrogel with controlled release of multi-type drugs for bone regeneration. Appl. Mater. Today 12, 294–308 (2018).
Liu, J. et al. Hydrogel-immobilized coacervate droplets as modular microreactor assemblies. Angew. Chem. Int. Ed. 59, 6853–6859 (2020).
Wang, H. et al. One-step generation of aqueous-droplet-filled hydrogel fibers as organoid carriers using an all-in-water microfluidic system. ACS Appl. Mater. Interfaces 13, 3199–3208 (2021).
Zhu, C., Itel, F., Chandrawati, R., Han, X. & Städler, B. Multicompartmentalized microreactors containing nuclei and catalase-loaded liposomes. Biomacromolecules 19, 4379–4385 (2018).
Guo, S. et al. Engineered living materials based on adhesin-mediated trapping of programmable cells. ACS Synth. Biol. 9, 475–485 (2020).
Ahn, S. H., Rath, M., Tsao, C. Y., Bentley, W. E. & Raghavan, S. R. Single-step synthesis of alginate microgels enveloped with a covalent polymeric shell: a simple way to protect encapsulated cells. ACS Appl. Mater. Interfaces 13, 18432–18442 (2021).
Walczak, M. et al. Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment. Nat. Commun. 12, 4743 (2021).
Westensee, I. N. et al. Mitochondria encapsulation in hydrogel-based artificial cells as ATP producing subunits. Small 17, 2007959 (2021).
Eun, Y. J., Utada, A. S., Copeland, M. F., Takeuchi, S. & Weibel, D. B. Encapsulating bacteria in agarose microparticles using microfluidics for high-throughput cell analysis and isolation. ACS Chem. Biol. 6, 260–266 (2011).
Tang, T. C. et al. Hydrogel-based biocontainment of bacteria for continuous sensing and computation. Nat. Chem. Biol. 17, 724–731 (2021).
Suzuka, J. et al. Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels. Nat. Biomed. Eng. 5, 914–925 (2021).
Qian, X., Westensee, I. N., Fernandes, C. C. & Städler, B. Enzyme mimic facilitated artificial cell to mammalian cell signal transfer. Angew. Chem. Int. Ed. 60, 18704–18711 (2021).
Juthani, N. & Doyle, P. S. A platform for multiplexed colorimetric microRNA detection using shape-encoded hydrogel particles. Analyst 145, 5134–5140 (2020).
Zeng, R., Huang, Z., Wang, Y. & Tang, D. Enzyme-encapsulated DNA hydrogel for highly efficient electrochemical sensing glucose. ChemElectroChem 7, 1537–1541 (2020).
Song, J. et al. Self-assembly of a magnetic DNA hydrogel as a new biomaterial for enzyme encapsulation with enhanced activity and stability. Chem. Commun. 55, 2449–2452 (2019).
Shin, D. S. et al. Synthesis of microgel sensors for spatial and temporal monitoring of protease activity. ACS Biomater. Sci. Eng. 4, 378–387 (2018).
Lee, K. et al. Multifunctional DNA nanogels for aptamer-based targeted delivery and stimuli-triggered release of cancer therapeutics. Macromol. Rapid Commun. 42, 2000457 (2021).
Zhang, H. et al. Cancer biomarker-triggered disintegrable DNA nanogels for intelligent drug delivery. Nano Lett. 20, 8399–8407 (2020).
Abdel-Fatah, T. M. A. et al. Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer. Mol. Oncol. 8, 1326–1338 (2014).
Ma, J. et al. Liposomes-camouflaged redox-responsive nanogels to resolve the dilemma between extracellular stability and intracellular drug release. Macromol. Biosci. 18, 1800049 (2018).
Hu, C. M. J. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980–10985 (2011).
Saleem, Q., Zhang, Z., Gradinaru, C. C. & MacDonald, P. M. Liposome-coated hydrogel spheres: delivery vehicles with tandem release from distinct compartments. Langmuir 29, 14603–14612 (2013).
Hanuš, J., Ullrich, M., Dohnal, J., Singh, M. & Štěpánek, F. Remotely controlled diffusion from magnetic liposome microgels. Langmuir 29, 4381–4387 (2013).
Hong, Y. J., Lee, H. Y. & Kim, J. C. Alginate beads containing pH-sensitive liposomes and glucose oxidase: glucose-sensitive release. Colloid Polym. Sci. 287, 1207–1214 (2009).
Volpatti, L. R. et al. Microgel encapsulated nanoparticles for glucose-responsive insulin delivery. Biomaterials 267, 120458 (2021).
Vader, P., Mol, E. A., Pasterkamp, G. & Schiffelers, R. M. Extracellular vesicles for drug delivery. Adv. Drug Deliv. Rev. 106, 148–156 (2016).
Fuhrmann, G. et al. Engineering extracellular vesicles with the tools of enzyme prodrug therapy. Adv. Mater. 30, 1706616 (2018).
Zhang, H., Koens, L., Lauga, E., Mourran, A. & Möller, M. A light-driven microgel rotor. Small 15, 1903379 (2019).
Alvarez, L. et al. Reconfigurable artificial microswimmers with internal feedback. Nat. Commun. 12, 4762 (2021).
Gao, N. et al. Chemical-mediated translocation in protocell-based microactuators. Nat. Chem. 13, 868–879 (2021).
Park, N., Um, S. H., Funabashi, H., Xu, J. & Luo, D. A cell-free protein-producing gel. Nat. Mater. 8, 432–437 (2009).
Whitfield, C. J. et al. Cell-free protein synthesis in hydrogel materials. Chem. Commun. 56, 7108–7111 (2020).
Benítez-Mateos, A. I. et al. Microcompartmentalized cell-free protein synthesis in hydrogel μ-channels. ACS Synth. Biol. 9, 2971–2978 (2020).
Park, N. et al. High-yield cell-free protein production from P-gel. Nat. Protoc. 4, 1759–1770 (2009).
Lee, K. H., Lee, K. Y., Byun, J. Y., Kim, B. G. & Kim, D. M. On-bead expression of recombinant proteins in an agarose gel matrix coated on a glass slide. Lab Chip 12, 1605–1610 (2012).
Byun, J. Y., Lee, K. H., Lee, K. Y., Kim, M. G. & Kim, D. M. In-gel expression and in situ immobilization of proteins for generation of three dimensional protein arrays in a hydrogel matrix. Lab Chip 13, 886–891 (2013).
Ouyang, X., Zhou, X., Lai, S. N., Liu, Q. & Zheng, B. Immobilization of proteins of cell extract to hydrogel networks enhances the longevity of cell-free protein synthesis and supports gene networks. ACS Synth. Biol. 10, 749–755 (2021).
Vibhute, M. A. et al. Transcription and translation in cytomimetic protocells perform most efficiently at distinct macromolecular crowding conditions. ACS Synth. Biol. 9, 2797–2807 (2020).
Yang, D. et al. Enhanced transcription and translation in clay hydrogel and implications for early life evolution. Sci. Rep. 3, 3165 (2013).
Hanczyc, M. M., Fujikawa, S. M. & Szostak, J. W. Experimental models of primitive cellular compartments: encapsulation, growth, and division. Science 302, 618–622 (2003).
Kahn, J. S. et al. DNA microgels as a platform for cell-free protein expression and display. Biomacromolecules 17, 2019–2026 (2016).
Jiao, Y., Liu, Y., Luo, D., Huck, W. T. S. & Yang, D. Microfluidic-assisted fabrication of clay microgels for cell-free protein synthesis. ACS Appl. Mater. Interfaces 10, 29308–29313 (2018).
Lai, S. N. et al. Artificial cells capable of long-lived protein synthesis by using aptamer grafted polymer hydrogel. ACS Synth. Biol. 9, 76–83 (2020).
Zhou, X., Wu, H., Cui, M., Lai, S. N. & Zheng, B. Long-lived protein expression in hydrogel particles: towards artificial cells. Chem. Sci. 9, 4275–4279 (2018).
Cui, J. et al. A PEGDA/DNA hybrid hydrogel for cell-free protein synthesis. Front. Chem. 8, 28 (2020).
Wang, C., Geng, Y., Sun, Q., Xu, J. & Lu, Y. A sustainable and efficient artificial microgel system: toward creating a configurable synthetic cell. Small 16, 2002313 (2020).
Nöth, M. et al. Biocatalytic microgels (μ-Gelzymes): synthesis, concepts, and emerging applications. Green Chem. 22, 8183–8209 (2020).
Lai, E., Wang, Y., Wei, Y., Li, G. & Ma, G. Covalent immobilization of trypsin onto thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) microspheres with high activity and stability. J. Appl. Polym. Sci. 133, 43343 (2016).
Welsch, N., Wittemann, A. & Ballauff, M. Enhanced activity of enzymes immobilized in thermoresponsive core-shell microgels. J. Phys. Chem. B 113, 16039–16045 (2009).
Wan, L. et al. Programmable self-assembly of DNA-protein hybrid hydrogel for enzyme encapsulation with enhanced biological stability. Biomacromolecules 17, 1543–1550 (2016).
Köhler, T. et al. Cell-free protein synthesis and: in situ immobilization of deGFP-MatB in polymer microgels for malonate-to-malonyl CoA conversion. RSC Adv. 10, 40588–40596 (2020).
Kleinschmidt, D. et al. Enhanced catalyst performance through compartmentalization exemplified by colloidal l-proline modified microgel catalysts. J. Colloid Interface Sci. 559, 76–87 (2020).
Mariconti, M., Morel, M., Baigl, D. & Rudiuk, S. Enzymatically active DNA-protein nanogels with tunable cross-linking density. Biomacromolecules 22, 3431–3439 (2021).
Singh, N., Lainer, B., Formon, G. J. M., De Piccoli, S. & Hermans, T. M. Re-programming hydrogel properties using a fuel-driven reaction cycle. J. Am. Chem. Soc. 142, 4083–4087 (2020).
Che, H., Buddingh’, B. C. & van Hest, J. C. M. Self-regulated and temporal control of a “breathing” microgel mediated by enzymatic reaction. Angew. Chem. Int. Ed. 56, 12581–12585 (2017).
Merindol, R., Martin, N., Beneyton, T., Baret, J. C. & Ravaine, S. Fast and ample light controlled actuation of monodisperse all-DNA microgels. Adv. Funct. Mater. 31, 2010396 (2021).
Song, J. et al. A RNA producing DNA hydrogel as a platform for a high performance RNA interference system. Nat. Commun. 9, 4331 (2018).
Song, J. et al. Living-DNA nanogel appendant enables in situ modulation and quantification of regulation effects on membrane proteins. ACS Appl. Bio Mater. 4, 4565–4574 (2021).
Simpson, L. W., Good, T. A. & Leach, J. B. Protein folding and assembly in confined environments: implications for protein aggregation in hydrogels and tissues. Biotechnol. Adv. 42, 107573 (2020).
Altamura, E. et al. Chromatophores efficiently promote light-driven ATP synthesis and DNA transcription inside hybrid multicompartment artificial cells. Proc. Natl Acad. Sci. USA 118, e2012170118 (2021).
Pérez-Luna, V. H. & González-Reynoso, O. Encapsulation of biological agents in hydrogels for therapeutic applications. Gels 4, 61 (2018).
Kanai, T., Nakai, H., Yamada, A., Fukuyama, M. & Weitz, D. A. Preparation of monodisperse hybrid gel particles with various morphologies via flow rate and temperature control. Soft Matter 15, 6934–6937 (2019).
Walker, S. A., Kennedy, M. T. & Zasadzinski, J. A. Encapsulation of bilayer vesicles by self-assembly. Nature 387, 61–64 (1997).
Shetty, S. C. et al. Directed signaling cascades in monodisperse artificial eukaryotic cells. ACS Nano 15, 15656–15666 (2021).
Buck, S. et al. Engineering lipobeads: properties of the hydrogel core and the lipid bilayer shell. Biomacromolecules 5, 2230–2237 (2004).
Lester, C. L., Smith, S. M., Colson, C. D. & Guymon, C. A. Physical properties of hydrogels synthesized from lyotropic liquid crystalline templates. Chem. Mater. 15, 3376–3384 (2003).
Saleem, Q., Liu, B., Gradinaru, C. C. & MacDonald, P. M. Lipogels: single-lipid-bilayer-enclosed hydrogel spheres. Biomacromolecules 12, 2364–2374 (2011).
Campbell, A., Taylor, P., Cayre, O. J. & Paunov, V. N. Preparation of aqueous gel beads coated by lipid bilayers. Chem. Comm. 21, 2378–2379 (2004).
Abele, T. et al. Two-photon 3D laser printing inside synthetic cells. Adv. Mater. 34, e2106709 (2022).
Walther, T., Jahnke, K., Abele, T. & Göpfrich, K. Printing and erasing of DNA-based photoresists inside synthetic cells. Adv. Funct. Mater. 32, 2200762 (2022).
Torres-Martínez, A., Angulo-Pachón, C. A., Galindo, F. & Miravet, J. F. Liposome-enveloped molecular nanogels. Langmuir 35, 13375–13381 (2019).
Martí-Centelles, R., Rubio-Magnieto, J. & Escuder, B. A minimalistic catalytically-active cell mimetic made of a supra-molecular hydrogel encapsulated into a polymersome. Chem. Commun. 56, 14487–14490 (2020).
Jesorka, A., Markström, M., Karlsson, M. & Orwar, O. Controlled hydrogel formation in the internal compartment of giant unilamellar vesicles. J. Phys. Chem. B 109, 14759–14763 (2005).
Huang, A. et al. BiobitsTM explorer: a modular synthetic biology education kit. Sci. Adv. 4, eaat5105 (2018).
De Geest, B. G. et al. Self-exploding lipid-coated microgels. Biomacromolecules 7, 373–379 (2006).
Kazakov, S., Kaholek, M., Teraoka, I. & Levon, K. UV-induced gelation on nanometer scale using liposome reactor. Macromolecules 35, 1911–1920 (2002).
Fern, J. & Schulman, R. Modular DNA strand-displacement controllers for directing material expansion. Nat. Commun. 9, 3766 (2018).
Wang, M. et al. Assembling responsive microgels at responsive lipid membranes. Proc. Natl Acad. Sci. USA 116, 5442–5450 (2019).
Kazakov, S. et al. Poly(N-isopropylacrylamide-co-1-vinylimidazole) hydrogel nanoparticles prepared and hydrophobically modified in liposome reactors: atomic force microscopy and dynamic light scattering study. Langmuir 19, 8086–8093 (2003).
Park, P. S. H. et al. Characterization of radioligand binding to a transmembrane receptor reconstituted into lipobeads. FEBS Lett. 567, 344–348 (2004).
Frank, P. et al. Proteo-lipobeads for the oriented encapsulation of membrane proteins. Soft Matter 11, 2906–2908 (2015).
Makhoul-Mansour, M. M. et al. A skin-inspired soft material with directional mechanosensation. Bioinspir. Biomim. 16, abf746 (2021).
Jia, H. et al. Shaping giant membrane vesicles in 3D-printed protein hydrogel cages. Small 16, 1906259 (2020).
Bansil, R., Stanley, E. & Thomas LaMont, J. Mucin biophysics. Annu. Rev. Physiol. 57, 635–657 (1995).
Costerton, J. W., Lewandowski, Z., Caldwell, D. E., Korber, D. R. & Lappin-Scott, H. M. Microbial biofilms. Annu. Rev. Microbiol. 49, 711–745 (1995).
Ahmadi, F., Oveisi, Z., Samani, M. & Amoozgar, Z. Chitosan based hydrogels: characteristics and pharmaceutical applications. Res. Pharm. Sci. 10, 1–16 (2015).
Sapra, K. T. & Bayley, H. Lipid-coated hydrogel shapes as components of electrical circuits and mechanical devices. Sci. Rep. 2, 848 (2012).
Falk, B., Garramone, S. & Shivkumar, S. Diffusion coefficient of paracetamol in a chitosan hydrogel. Mater. Lett. 58, 3261–3265 (2004).
Amsden, B. Solute diffusion within hydrogels. Mechanisms models. Macromolecules 31, 8382–8395 (1998).
Sandrin, D. et al. Diffusion of macromolecules in a polymer hydrogel: from microscopic to macroscopic scales. Phys. Chem. Chem. Phys. 18, 12860–12876 (2016).
Czerner, M., Fellay, L. S., Suárez, M. P., Frontini, P. M. & Fasce, L. A. Determination of elastic modulus of gelatin gels by indentation experiments. Procedia Mater. Sci. 8, 287–296 (2015).
Bromberg, L. Scaling of rheological properties of hydrogels from associating polymers. Macromolecules 31, 6148–6156 (1998).
Atik, A. F. et al. Hyaluronic acid based low viscosity hydrogel as a novel carrier for convection enhanced delivery of CAR T cells. J. Clin. Neurosci. 56, 163–168 (2018).
Korson, L., Drost-Hansen, W. & Millero, F. J. Viscosity of water at various temperatures. J. Phys. Chem. 73, 34–39 (1969).
Fushimi, K. & Verkman, A. S. Low viscosity in the aqueous domain of cell cytoplasm measured by picosecond polarization microfluorimetry. J. Cell Biol. 112, 719–725 (1991).
Liu, H. et al. In situ mechanical characterization of the cell nucleus by atomic force microscopy. ACS Nano 8, 3821–3828 (2014).
Novak, I. L., Kraikivski, P. & Slepchenko, B. M. Diffusion in cytoplasm: effects of excluded volume due to internal membranes and cytoskeletal structures. Biophys. J. 97, 758–767 (2009).
Gardel, M. L., Kasza, K. E., Brangwynne, C. P., Liu, J. & Weitz, D. A. Chapter 19: mechanical response of cytoskeletal networks. Methods Cell Biol. 89, 487–519 (2008).
Kihara, T., Ito, J. & Miyake, J. Measurement of biomolecular diffusion in extracellular matrix condensed by fibroblasts using fluorescence correlation spectroscopy. PLoS ONE 8, 82382 (2013).
Nebuloni, M. et al. Insight on colorectal carcinoma infiltration by studying perilesional extracellular matrix. Sci. Rep. 6, 22522 (2016).
Fernández-Pérez, J. & Ahearne, M. The impact of decellularization methods on extracellular matrix derived hydrogels. Sci. Rep. 9, 14933 (2019).
Jalalvandi, E., Hanton, L. R. & Moratti, S. C. Schiff-base based hydrogels as degradable platforms for hydrophobic drug delivery. Eur. Polym. J. 90, 13–24 (2017).
Okudan, A. & Altay, A. Investigation of the effects of different hydrophilic and hydrophobic comonomers on the volume phase transition temperatures and thermal properties of N-isopropylacrylamide-based hydrogels. Int. J. Polym. Sci. 2019, 7324181 (2019).
Wang, Y. et al. Chitosan cross-linked poly(acrylic acid) hydrogels: drug release control and mechanism. Colloids Surf. B Biointerfaces 152, 252–259 (2017).
Katono, H., Sanui, K., Ogata, N., Okano, T. & Sakurai, Y. On-off drug release mechanism from thermo-responsive IPNs composed of poly(acrylamide-co-butyl methacrylate) and poly(acrylic acid). Jpn J. Artif. Organs 21, 239–243 (1992).
Burmistrova, A., Richter, M., Uzum, C. & Klitzing, R. V. Effect of cross-linker density of P(NIPAM-co-AAc) microgels at solid surfaces on the swelling/shrinking behaviour and the Young’s modulus. Colloid Polym. Sci. 289, 613–624 (2011).
Kong, H. J., Alsberg, E., Kaigler, D., Lee, K. Y. & Mooney, D. J. Controlling degradation of hydrogels via the size of cross-linked junctions. Adv. Mater. 16, 1917–1921 (2004).
Ashraf, S., Park, H. K., Park, H. & Lee, S. H. Snapshot of phase transition in thermoresponsive hydrogel PNIPAM: role in drug delivery and tissue engineering. Macromol. Res. 24, 297–304 (2016).
Kim, A., Mujumdar, S. K. & Siegel, R. A. Swelling properties of hydrogels containing phenylboronic acids. Chemosensors 2, 1–12 (2014).
Acknowledgements
This work was supported by a UK Research and Innovation (UKRI) Future Leaders Fellowship, grant reference number MR/S031537/1 (awarded to Y.E.); an Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training Studentship from the Institute of Chemical Biology, grant reference number EP/S023518 (awarded to M.E.A.), an EPSRC Doctoral Prize Fellowship (awarded to J.W.H.) and an EPSRC grant, reference number EP/V048651/1.
Author information
Authors and Affiliations
Contributions
M.E.A., J.W.H. and Y.E. proposed the framework of this Review. All authors contributed through researching, writing and editing the Review.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature Reviews Chemistry thanks the anonymous reviewers for their contribution to the peer review of this work.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Glossary
- Artificial cell
-
An engineered device that attempts to mimic the form, function and/or behaviours of biological cells.
- Synthetic biology
-
A field that involves the redesign of existing organisms (top down) or the construction of new cell-like entities from molecular building blocks (bottom up).
- Vesicle
-
Aqueous compartment coated with a bilayer of amphiphilic molecules (usually lipids).
- Coacervates
-
A colloid rich aqueous phase that is formed through liquid–liquid phase separation.
- Nanogel
-
A nanoparticle (nanometre size) that comprises a hydrogel network.
- Microgel
-
A microparticle (micrometre size) that comprises a hydrogel network.
- Droplet interface bilayer
-
(DIB). A lipid bilayer that is formed between aqueous droplets in oil from the contact of water–oil interfaces in the presence of a suitable phospholipid.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Allen, M.E., Hindley, J.W., Baxani, D.K. et al. Hydrogels as functional components in artificial cell systems. Nat Rev Chem 6, 562–578 (2022). https://doi.org/10.1038/s41570-022-00404-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41570-022-00404-7
This article is cited by
-
Artificial cells for in vivo biomedical applications through red blood cell biomimicry
Nature Communications (2024)
-
Biomimetic cell encapsulations by microfluidics
Science China Materials (2024)
-
Monolithic-to-focal evolving biointerfaces in tissue regeneration and bioelectronics
Nature Chemical Engineering (2024)
-
Phase-separation facilitated one-step fabrication of multiscale heterogeneous two-aqueous-phase gel
Nature Communications (2023)