Artificial cells with viscoadaptive behavior based on hydrogel-loaded giant unilamellar vesicles

Antoni Llopis-Lorente, Maaike J.G. Schotman, Heorhii V. Humeniuk, Jan C.M. van Hest (Corresponding author), Patricia Y.W. Dankers (Corresponding author), Loai K.E.A. Abdelmohsen (Corresponding author)

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Viscoadaptation is an essential process in natural cells, where supramolecular interactions between cytosolic components drive adaptation of the cellular mechanical features to regulate metabolic function. This important relationship between mechanical properties and function has until now been underexplored in artificial cell research. Here, we have created an artificial cell platform that exploits internal supramolecular interactions to display viscoadaptive behavior. As supramolecular material to mimic the cytosolic component of these artificial cells, we employed a pH-switchable hydrogelator based on poly(ethylene glycol) coupled to ureido-pyrimidinone units. The hydrogelator was membranized in its sol state in giant unilamellar lipid vesicles to include a cell-membrane mimetic component. The resulting hydrogelator-loaded giant unilamellar vesicles (designated as HL-GUVs) displayed reversible pH-switchable sol-gel behavior through multiple cycles. Furthermore, incorporation of the regulatory enzyme urease enabled us to increase the cytosolic pH upon conversion of its substrate urea. The system was able to switch between a high viscosity (at neutral pH) and a low viscosity (at basic pH) state upon addition of substrate. Finally, viscoadaptation was achieved via the incorporation of a second enzyme of which the activity was governed by the viscosity of the artificial cell. This work represents a new approach to install functional self-regulation in artificial cells, and opens new possibilities for the creation of complex artificial cells that mimic the structural and functional interplay found in biological systems.

Original languageEnglish
Pages (from-to)629-638
Number of pages10
JournalChemical Science
Issue number2
Publication statusPublished - 14 Jan 2024


The authors would like to acknowledge the support from the Dutch Ministry of Education, Culture, and Science (Gravitation programs 024.001.035, 024.003.013, 024.005.020 - Interactive Polymer Materials IPM, and the Spinoza premium), from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON2014-27 REMAIN, and the ERC Advanced Grant (Artisym 694120). A. L.-L. acknowledges support from the MSCA Cofund project oLife, which has received funding from the European Union's Horizon 2020 research and innovation program under the Grant Agreement 847675. A. L.-L. thanks the Spanish Government for his ‘Ramón y Cajal’ grant (RYC2021-034728-I), funded by MCIN/AEI/10.13039/501100011033 and by the European Union «NextGenerationEU»/«PRTR». A. L.-L. also thanks funding by Ayuda para potenciar la investigación postdoctoral de la UPV (PAID-PD-22), and Ayuda a Primeros Proyectos de Investigación (PAID-06-22), Vicerrectorado de Investigación de la Universitat Politècnica de València (UPV).

FundersFunder number
Dutch Ministry of Education, Culture, and Science024.005.020, 024.003.013, 024.001.035
Interactive Polymer Materials IPM
Marie Skłodowska‐Curie
European CommissionPAID-PD-22, PAID-06-22
European Research Council694120
Universidad Politécnia de Valencia
Horizon 2020MCIN/AEI/10.13039/501100011033, RYC2021-034728-I, 847675


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