Size-controlled assembly of phase separated protein condensates with interfacial protein cages

Abstract Phase separation of specific proteins into liquid-like condensates is a key mechanism for forming membrane-less organelles, which organize diverse cellular processes in space and time. These protein condensates hold immense potential as biomaterials capable of containing specific sets of bi...

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Main Authors: Hyeok Jin Oh, Yongsuk Lee, Haerang Hwang, Kibeom Hong, Hyeongjoo Choi, Jin Young Kang, Yongwon Jung
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56391-y
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author Hyeok Jin Oh
Yongsuk Lee
Haerang Hwang
Kibeom Hong
Hyeongjoo Choi
Jin Young Kang
Yongwon Jung
author_facet Hyeok Jin Oh
Yongsuk Lee
Haerang Hwang
Kibeom Hong
Hyeongjoo Choi
Jin Young Kang
Yongwon Jung
author_sort Hyeok Jin Oh
collection DOAJ
description Abstract Phase separation of specific proteins into liquid-like condensates is a key mechanism for forming membrane-less organelles, which organize diverse cellular processes in space and time. These protein condensates hold immense potential as biomaterials capable of containing specific sets of biomolecules with high densities and dynamic liquid properties. Despite their appeal, methods to manipulate protein condensate materials remain largely unexplored. Here, we present a one-pot assembly method to assemble coalescence-resistant protein condensates, ranging from a few μm to 100 nm in sizes, with surface-stabilizing protein cages. We discover that large protein cages (~30 nm), finely tuned to interact with condensates, efficiently localize on condensate surfaces and prevent the merging (coalescence) of condensates during phase separation. We precisely control condensate diameters by modulating condensate/cage ratios. In addition, the 3D structures of intact protein condensates with interfacial cages are visualized with cryo-electron tomography (ET). This work offers a versatile platform for designing size-controlled, surface-engineered protein condensate materials.
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publishDate 2025-01-01
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spelling doaj-art-ee4b74de85a04955b3ebb5b70ab0633a2025-01-26T12:41:00ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-56391-ySize-controlled assembly of phase separated protein condensates with interfacial protein cagesHyeok Jin Oh0Yongsuk Lee1Haerang Hwang2Kibeom Hong3Hyeongjoo Choi4Jin Young Kang5Yongwon Jung6Department of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyDepartment of Chemistry, Korea Advanced Institute of Science and TechnologyAbstract Phase separation of specific proteins into liquid-like condensates is a key mechanism for forming membrane-less organelles, which organize diverse cellular processes in space and time. These protein condensates hold immense potential as biomaterials capable of containing specific sets of biomolecules with high densities and dynamic liquid properties. Despite their appeal, methods to manipulate protein condensate materials remain largely unexplored. Here, we present a one-pot assembly method to assemble coalescence-resistant protein condensates, ranging from a few μm to 100 nm in sizes, with surface-stabilizing protein cages. We discover that large protein cages (~30 nm), finely tuned to interact with condensates, efficiently localize on condensate surfaces and prevent the merging (coalescence) of condensates during phase separation. We precisely control condensate diameters by modulating condensate/cage ratios. In addition, the 3D structures of intact protein condensates with interfacial cages are visualized with cryo-electron tomography (ET). This work offers a versatile platform for designing size-controlled, surface-engineered protein condensate materials.https://doi.org/10.1038/s41467-025-56391-y
spellingShingle Hyeok Jin Oh
Yongsuk Lee
Haerang Hwang
Kibeom Hong
Hyeongjoo Choi
Jin Young Kang
Yongwon Jung
Size-controlled assembly of phase separated protein condensates with interfacial protein cages
Nature Communications
title Size-controlled assembly of phase separated protein condensates with interfacial protein cages
title_full Size-controlled assembly of phase separated protein condensates with interfacial protein cages
title_fullStr Size-controlled assembly of phase separated protein condensates with interfacial protein cages
title_full_unstemmed Size-controlled assembly of phase separated protein condensates with interfacial protein cages
title_short Size-controlled assembly of phase separated protein condensates with interfacial protein cages
title_sort size controlled assembly of phase separated protein condensates with interfacial protein cages
url https://doi.org/10.1038/s41467-025-56391-y
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