Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells

Protocells offer a versatile material for dissecting cellular processes and developing simplified biomimetic systems by combining biological components with synthetic ones. However, a gap exists between the integrity and complex functionality of native organelles such as nuclei, and bottom‐up strate...

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Main Authors: Lukas Heuberger, Arianna Balestri, Shabnam Tarvirdipour, Larisa E. Kapinos, Roderick Y. H. Lim, Emanuel Lörtscher, Cora‐Ann Schoenenberger, Cornelia G. Palivan
Format: Article
Language:English
Published: Wiley-VCH 2025-06-01
Series:Small Science
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Online Access:https://doi.org/10.1002/smsc.202400622
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author Lukas Heuberger
Arianna Balestri
Shabnam Tarvirdipour
Larisa E. Kapinos
Roderick Y. H. Lim
Emanuel Lörtscher
Cora‐Ann Schoenenberger
Cornelia G. Palivan
author_facet Lukas Heuberger
Arianna Balestri
Shabnam Tarvirdipour
Larisa E. Kapinos
Roderick Y. H. Lim
Emanuel Lörtscher
Cora‐Ann Schoenenberger
Cornelia G. Palivan
author_sort Lukas Heuberger
collection DOAJ
description Protocells offer a versatile material for dissecting cellular processes and developing simplified biomimetic systems by combining biological components with synthetic ones. However, a gap exists between the integrity and complex functionality of native organelles such as nuclei, and bottom‐up strategies reducing cellular functions within a synthetic environment. Here, this gap is bridged by incorporating native nuclei into polymeric giant unilamellar vesicles (pGUVs) using double‐emulsion microfluidics. It is shown that the nuclei retain their morphology and nuclear envelope integrity, facilitating the import of co‐encapsulated peptide‐based multicompartment micelles (MCMs) via nuclear localization signals (NLS). Importantly, it is demonstrated that the nuclear import machinery remains functional inside the protocells, and by enriching the GUV interior with nuclear import‐promoting factors, the delivery efficiency of NLS‐MCMs significantly increases. The findings reveal that nucleated protocells preserve nuclear function and integrity for extended periods, providing a new platform for studying nuclear processes in a simplified, yet biologically relevant, environment. This approach opens avenues for creating advanced biohybrid materials, offering opportunities to investigate organelle behavior and their interactions with cellular components in greater detail. The findings establish a foundation for high‐throughput applications in synthetic biology and contribute valuable insights into sustaining complex cellular functions in engineered systems.
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spelling doaj-art-e27c96f758e04d88a2abb89a1675bf132025-08-20T02:06:26ZengWiley-VCHSmall Science2688-40462025-06-0156n/an/a10.1002/smsc.202400622Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in ProtocellsLukas Heuberger0Arianna Balestri1Shabnam Tarvirdipour2Larisa E. Kapinos3Roderick Y. H. Lim4Emanuel Lörtscher5Cora‐Ann Schoenenberger6Cornelia G. Palivan7Department of Chemistry University of Basel Mattenstrasse 22 4058 Basel SwitzerlandDepartment of Chemistry University of Basel Mattenstrasse 22 4058 Basel SwitzerlandDepartment of Chemistry University of Basel Mattenstrasse 22 4058 Basel SwitzerlandBiozentrum and Swiss Nanoscience Institute University of Basel Spitalstrasse 41 4056 Basel SwitzerlandBiozentrum and Swiss Nanoscience Institute University of Basel Spitalstrasse 41 4056 Basel SwitzerlandIBM Research Europe–Zürich Säumerstrasse 4 8803 Rüschlikon SwitzerlandDepartment of Chemistry University of Basel Mattenstrasse 22 4058 Basel SwitzerlandDepartment of Chemistry University of Basel Mattenstrasse 22 4058 Basel SwitzerlandProtocells offer a versatile material for dissecting cellular processes and developing simplified biomimetic systems by combining biological components with synthetic ones. However, a gap exists between the integrity and complex functionality of native organelles such as nuclei, and bottom‐up strategies reducing cellular functions within a synthetic environment. Here, this gap is bridged by incorporating native nuclei into polymeric giant unilamellar vesicles (pGUVs) using double‐emulsion microfluidics. It is shown that the nuclei retain their morphology and nuclear envelope integrity, facilitating the import of co‐encapsulated peptide‐based multicompartment micelles (MCMs) via nuclear localization signals (NLS). Importantly, it is demonstrated that the nuclear import machinery remains functional inside the protocells, and by enriching the GUV interior with nuclear import‐promoting factors, the delivery efficiency of NLS‐MCMs significantly increases. The findings reveal that nucleated protocells preserve nuclear function and integrity for extended periods, providing a new platform for studying nuclear processes in a simplified, yet biologically relevant, environment. This approach opens avenues for creating advanced biohybrid materials, offering opportunities to investigate organelle behavior and their interactions with cellular components in greater detail. The findings establish a foundation for high‐throughput applications in synthetic biology and contribute valuable insights into sustaining complex cellular functions in engineered systems.https://doi.org/10.1002/smsc.202400622native nucleinuclear deliverypeptide multicompartment micellespolymeric GUVsprotocells
spellingShingle Lukas Heuberger
Arianna Balestri
Shabnam Tarvirdipour
Larisa E. Kapinos
Roderick Y. H. Lim
Emanuel Lörtscher
Cora‐Ann Schoenenberger
Cornelia G. Palivan
Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
Small Science
native nuclei
nuclear delivery
peptide multicompartment micelles
polymeric GUVs
protocells
title Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
title_full Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
title_fullStr Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
title_full_unstemmed Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
title_short Polymeric Giant Unilamellar Vesicles Support Longevity of Native Nuclei in Protocells
title_sort polymeric giant unilamellar vesicles support longevity of native nuclei in protocells
topic native nuclei
nuclear delivery
peptide multicompartment micelles
polymeric GUVs
protocells
url https://doi.org/10.1002/smsc.202400622
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